Racking the brain: detection of cerebral edema on postmortem computed tomography compared with forensic autopsy

PURPOSE The purpose of this study was to compare postmortem computed tomography with forensic autopsy regarding their diagnostic reliability of differentiating between pre-existing cerebral edema and physiological postmortem brain swelling. MATERIALS AND METHODS The study collective included a total of 109 cases (n=109/200, 83 male, 26 female, mean age: 53.2 years) and were retrospectively evaluated for the following parameters (as related to the distinct age groups and causes of death): tonsillar herniation, the width of the outer and inner cerebrospinal fluid spaces and the radiodensity measurements (in Hounsfield Units) of the gray and white matter. The results were compared with the findings of subsequent autopsies as the gold standard for diagnosing cerebral edema. p-Values <0.05 were considered statistically significant. RESULTS Cerebellar edema (despite normal postmortem swelling) can be reliably assessed using postmortem computed tomography and is indicated by narrowed temporal horns and symmetrical herniation of the cerebellar tonsils (p<0.001). There was a significant difference (p<0.001) between intoxication (or asphyxia) and all other causes of death; the former causes demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units), and the gray to white matter ratio was >1.58 when leukoencephalopathy was excluded. CONCLUSIONS Despite normal postmortem changes, generalized brain edema can be differentiated on postmortem computed tomography, and white and gray matter Hounsfield measurements help to determine the cause of death in cases of intoxication or asphyxia. Racking the brain about feasible applications for a precise and reliable brain diagnostic forensic radiology method has just begun.

Brain barriers: Crosstalk between complex tight junctions and adherens junctions

Unique intercellular junctional complexes between the central nervous system (CNS) microvascular endothelial cells and the choroid plexus epithelial cells form the endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid barrier (BCSFB), respectively. These barriers inhibit paracellular diffusion, thereby protecting the CNS from fluctuations in the blood. Studies of brain barrier integrity during development, normal physiology, and disease have focused on BBB and BCSFB tight junctions but not the corresponding endothelial and epithelial adherens junctions. The crosstalk between adherens junctions and tight junctions in maintaining barrier integrity is an understudied area that may represent a promising target for influencing brain barrier function.

Endoscopic Biopsy for Intra- and Paraventricular Tumors: Rates of Complications, Mortality, and Tumor Cell Dissemination

Background and Study Aim Intra- and paraventricular tumors are frequently associated with cerebrospinal fluid (CSF) pathway obstruction. Thus the aim of an endoscopic approach is to restore patency of the CSF pathways and to obtain a tumor biopsy. Because endoscopic tumor biopsy may increase tumor cell dissemination, this study sought to evaluate this risk. Patients, Materials, and Methods Forty-four patients who underwent endoscopic biopsies for ventricular or paraventricular tumors between 1993 and 2011 were included in the study. Charts and images were reviewed retrospectively to evaluate rates of adverse events, mortality, and tumor cell dissemination. Adverse events, mortality, and tumor cell dissemination were evaluated. Results Postoperative clinical condition improved in 63.0% of patients, remained stable in 30.4%, and worsened in 6.6%. One patient (2.2%) had a postoperative thalamic stroke leading to hemiparesis and hemineglect. No procedure-related deaths occurred. Postoperative tumor cell dissemination was observed in 14.3% of patients available for follow-up. Conclusions For patients presenting with occlusive hydrocephalus due to tumors in or adjacent to the ventricular system, endoscopic CSF diversion is the procedure of first choice. Tumor biopsy in the current study did not affect safety or efficacy.

THE RELATIONSHIP BETWEEN THE RHEOENCEPHALOGRAM AND CEREBRAL BLOOD FLOW

The rheoencephalogram (REG) is the change in the electrical impedance of the head that occurs with each heart beat. Without knowledge of the relationship between cerebral blood flow (Q) and the REG, the utility of the REG in the study of the cerebral vasculature is greatly limited. The hypothesis is that the relationship between the REG and Q when venous outflow is nonpulsatile is^ (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)^ where K is a proportionality constant and Q is the mean Q.^ Pulsatile CBF was measured in the goat via a chronically implanted electromagnetic flowmeter. Electrodes were implanted in the ipsilateral cerebral hemisphere, and the REG was measured with a two electrode impedance plethysmograph. Measurements were made with the animal's head elevated so that venous flow pulsations were not transmitted from the heart to the cerebral veins. Measurements were made under conditions of varied cerebrovascular resistance induced by altering blood CO(,2) levels and under conditions of high and low cerebrospinal fluid pressures. There was a high correlation (r = .922-.983) between the REG calculated from the hypothesized relationship and the measured REG under all conditions.^ Other investigators have proposed that the REG results from linear changes in blood resistivity proportional to blood velocity. There was little to no correlation between the measured REG and the flow velocity ( r = .022-.306). A linear combination of the flow velocity and the hypothesized relationship between the REG and Q did not predict the measured REG significantly better than the hypothesized relationship alone in 37 out of 50 experiments.^ Jacquy proposed an index (F) of cerebral blood flow calculated from amplitudes and latencies of the REG. The F index was highly correlated (r = .929) with measured cerebral blood flow under control and hypercapnic conditions, but was not as highly correlated under conditions of hypocapnia (r = .723) and arterial hypotension (r = .681).^ The results demonstrate that the REG is not determined by mean cerebral blood flow, but by the pulsatile flow only. Thus, the utility of the REG in the determination of mean cerebral blood flow is limited. ^

Emerging arboviruses in Harris County, Texas

Harris County, which includes Houston, Texas, is an endemic and epidemic area for two viruses transmitted by arthropods (arboviruses). These viruses are maintained in cycles involving mosquitoes and wild birds, and transmission to humans is accidental. The majority of human infections is asymptomatic or may result in a flu-like syndrome. However, some infections can result in meningitis or encephalitis. These neuroinvasive infections may cause death, and those who survive may experience serious neurological complications requiring costly and lengthy medical care. The most important arboviruses in terms of morbidity are St. Louis encephalitis (SLEV) and West Nile (WNV) viruses. In fact, Harris County reports more SLEV encephalitis cases than any other county in the U.S. Most arboviral human cases occur from July through September, when mosquitoes are most active. Those at risk for encephalitis and death are the elderly and those with a history of hypertension or immunosuppresion. There is no specific treatment and no human vaccines are commercially available in the U.S. The approach for control of arboviruses in Harris County during epidemics is multidisciplinary and executed by several agencies. It includes surveillance, vector control, and educational messages for the population. Prevention of outbreaks consists of elimination of the vector and its breeding grounds, and practicing personal protective measures to prevent exposure to mosquitoes. ^ Current findings indicate that mosquito-borne viruses other than SLEV and WNV could pose an additional threat for the population. Eastern equine encephalitis virus (EEEV) activity has been detected in dogs and sentinel chickens in Houston and surrounding areas. Several serotypes of dengue virus have caused recent outbreaks in south Texas, and some locally-acquired cases have been detected in Houston. Since the clinical presentation of all arboviruses that cause encephalitis is very similar, and current surveillance is focused on detecting SLEV and WNV, there is a possibility that other arboviruses could be present in the area but are not being detected. Additionally, Harris County's ample annual rainfall and flooding problems, warm weather, multiple mosquito species, local and migrating birds that are susceptible to arboviral infection, and a constant flow of goods and travelers from many parts of the world could favor the emergence or re-emergence of other arboviruses. ^ The aims of this project were to determine if other arboviruses were circulating in the county, to assess the knowledge and attitudes about mosquito-borne viruses in a sample of the population, and to conduct an analysis of the initial WNV epidemic in Harris County. Through the retrospective analysis of clinical specimens collected during the 2002-2005 epidemic seasons, serologic evidence of dengue infection was detected suggesting the possibility that this virus may be co-circulating with SLEV and WNV. A cross-sectional survey revealed high awareness about arboviruses but not a consistent use of protective measures to avoid mosquitoes. The third component for this project included a retrospective review and geographical analysis of the 2002 WNV epidemic. ^ Overall, this study documented valuable information about the dengue virus, a potentially emerging arbovirus in Texas, revealed the need for more educational preventative programs, reinforced the value of mosquito and avian surveillance, and indicated the importance of continuing to investigate the factors that contribute to the development of outbreaks. ^

Defining barriers in caring for seriously-ill children in a resource-limited setting: An observational study of 2 children's hospitals in Haiti

Background. According to the WHO 2007 country report, Haiti lags behind the Millennium Development Goal of reducing child mortality and maintains the highest under-5 mortality rate in the Western hemisphere. 3 Overall, few studies exist that seek to better grasp barriers in caring for a seriously ill child in a resource-limited setting and only a handful propose sustainable, effective interventions. ^ Objectives. The objectives of this study are to describe the prevalence of serious illnesses among children hospitalized at 2 children's hospitals in Port au Prince, to determine the barriers faced when caring for seriously ill children, and to report hospital outcomes of children admitted with serious illnesses. ^ Methods. Data were gathered from 2 major children's hospitals in Port au Prince, Haiti (Grace Children's Hospital [GCH] and Hopital d l'Universite d'Etat d'Haiti [HUEH]) using a triangulated approach of focus group discussions, physician questionnaires, and retrospective chart review. 23 pediatric physicians participated in focus group discussions and completed a self-administered questionnaire evaluating healthcare provider knowledge, self-efficacy, and perceived barriers relating to the care of seriously ill children in a resource-limited setting. A sample of 240 patient charts meeting eligibility criteria was abstracted for pertinent elements including sociodemographics, documentation, treatment strategies, and outcomes. Factors associated with mortality were analyzed using χ2 test and Fisher exact test [Minitab v.15]. ^ Results. The most common primary diagnoses at admission were gastroenteritis with moderate dehydration (35.5%), severe malnutrition (25.8%), and pneumonia (19.3%) for GCH, and severe malnutrition (32.6%), sepsis (24.7%), and severe respiratory distress (18%) for HUEH. Overall, 12.9% and 27% of seriously ill patients presented with shock to GCH and HUEH, respectively. ^ Shortage of necessary materials and equipment represented the most commonly reported limitation (18/23 respondents). According to chart data, 9.4% of children presenting with shock did not receive a fluid bolus, and only 8% of patients presenting with altered mental status or seizures received a glucose check. 65% of patients with meningitis did not receive a lumbar puncture due to lack of materials. ^ Hospital mortality rates did not differ by gender or by institution. Children who died were more likely to have a history of prematurity (OR 4.97 [95% CI 1.32-18.80]), an incomplete vaccination record (OR 4.05 [95% CI 1.68-9.74]), or a weight for age ≤3rd percentile (OR 6.1 [95% CI 2.49-14.93]. Case-fatality rates were significantly higher among those who presented with signs of shock compared with those who did not (23.1% vs. 10.7%, RR=2.16, p=0.03). Caregivers did not achieve shock reversal in 21% of patients and did not document shock reversal in 50% of patients. ^ Conclusions. Many challenges face those who seek to optimize care for seriously ill children in resource-limited settings. Specifically, in Haiti, qualitative and quantitative data suggest major issues with lack of supplies, pre-hospital factors, including malnutrition as a comorbidity, and early recognition and management of shock. A tailored intervention designed to address these issues is needed in order to prospectively evaluate improvements in child mortality in a high-risk population.^

Risk factors for encephalitis and death from West Nile virus infection: An analysis of hospitalized cases in Houston, Texas from 2002--2008

We conducted a nested case-control study to determine the significant risk factors for developing encephalitis from West Nile virus (WNV) infection. The purpose of this research project was to expand the previously published Houston study of 2002–2004 patients to include data on Houston patients from four additional years (2005–2008) to determine if there were any differences in risk factors shown to be associated with developing the more severe outcomes of WNV infection, encephalitis and death, by having this larger sample size. A re-analysis of the risk factors for encephalitis and death was conducted on all of the patients from 2002–2008 and was the focus of this proposed research. This analysis allowed for the determination to be made that there are differences in the outcome in the risk factors for encephalitis and death with an increased sample size. Retrospective medical chart reviews were completed for the 265 confirmed WNV hospitalized patients; 153 patients had encephalitis (WNE), 112 had either viral syndrome with fever (WNF) or meningitis (WNM); a total of 22 patients died. Univariate logistic regression analyses on demographic, comorbidities, and social risk factors was conducted in a similar manner as in the previously conducted study to determine the risk factors for developing encephalitis from WNV. A multivariate model was developed by using model building strategies for the multivariate logistic regression analysis. The hypothesis of this study was that there would be additional risk factors shown to be significant with the increase in sample size of the dataset. This analysis with a greater sample size and increased power supports the hypothesis in that there were additional risk factors shown to be statistically associated with the more severe outcomes of WNV infection (WNE or death). Based on univariate logistic regression results, these data showed that even though age of 20–44 years was statistically significant as a protecting effect for developing WNE in the original study, the expanded sample lacked significance. This study showed a significant WNE risk factor to be chronic alcohol abuse, when it was not significant in the original analysis. Other WNE risk factors identified in this analysis that showed to be significant but were not significant in the original analysis were cancer not in remission > 5 years, history of stroke, and chronic renal disease. When comparing the two analyses with death as an outcome, two risk factors that were shown to be significant in the original analysis but not in the expanded dataset analysis were diabetes mellitus and immunosuppression. Three risk factors shown to be significant in this expanded analysis but were not significant in the original study were illicit drug use, heroin or opiate use, and injection drug use. However, with the multiple logistic regression models, the same independent risk factors for developing encephalitis of age and history of hypertension including drug induced hypertension were consistent in both studies.^

Suspected outbreak of dengue fever in Houston: Clinical characteristics and determination of autochthonous transmission between 2003 and 2005

Houston, Texas maintains the appropriate climate and mosquito populations to support the circulation of dengue viruses. The city is susceptible to the introduction and subsequent local transmission of dengue virus with its proximity to dengue-endemic Mexico and the high degree of international travel routed through its airports. In 2008, a study at the University of Texas School of Public Health identified 58 suspected dengue fever cases that presented at hospitals and clinics in the Houston area. Serum or CSF samples of the 58 samples tested positive or equivocal for the presence of anti-dengue IgM antibodies (Rodriguez, 2008). Here, we present the results of an investigation aimed to describe the clinical characteristics of the 58 suspected dengue fever cases and to determine if local transmission had occurred. Data from medical record abstractions and personal telephone interviews were used to describe clinical characteristics and travel history of the suspected cases. Our analysis classified six probable dengue fever cases based on the case definition from the World Health Organization. Three of the probable cases for which we were able to obtain travel history had not recently traveled to an endemic area prior to onset of symptoms suggesting the illnesses were locally acquired in Houston. Further analysis led us to hypothesize that additional cases of dengue fever are present in our study population. Fifty-one percent of the study population was diagnosed with meningitis and/or encephalitis. Sixty percent of the individuals who received a lumbar puncture had abnormal CSF. Together these findings indicate viral infection with neurological involvement, which has been reported to occur with dengue fever. Among the individuals who received liver enzyme analysis, 54% had evidence of abnormal liver enzyme levels, a clinical sign commonly observed with dengue. Our results indicate that a suspected outbreak of dengue fever with autochthonous transmission occurred in the Houston area between 2003 and 2005. ^

A case-control study of the risk factors for eclampsia

Objective. To study the risk factors for eclampsia, a rare but significant complication of pregnancy.^ Target population. All deliveries at or after the 20th week of gestation that took place between January 1, 1977 and March 1992, and between January 1990 and April 1992 at two hospitals in Houston, Texas, respectively.^ Study population. Sixty-six confirmed cases of eclampsia, and 2 groups of randomly selected controls: Non-preeclamptic and preeclamptic deliveries matched to cases on hospital and month of delivery on a 1:4 ratio.^ Exclusions. Women with chronic hypertension, gestational epilepsy, a previous history of epilepsy, and convulsions attributed to encephalitis, meningitis, cerebral tumor, and intracerebral bleeding, and women without a definite diagnosis of preeclampsia/eclampsia.^ Results. Eclampsia developed in 0.52-0.93/1000 deliveries. Fifty-six percent of seizures occurred in the antepartum period, 2% as early as 20 weeks of gestation and 39% between 37 and 42 weeks. Twenty-nine percent and 15% occurred in the postpartum and late postpartum periods, respectively, 8% as late as one week postpartum. A different set of risk factors was involved in the development of eclampsia in non-preeclamptic women than in the progression from preeclampsia to eclampsia. Factors involved in the development of eclampsia included, in addition to twin pregnancy and family history of pregnancy-induced hypertension, fewer than 3 prenatal care visits, urinary tract infections, primigravidity, obesity, black ethnicity, diabetes mellitus, and age $\le$20 years. Risk factors involved in the progression from preeclampsia to eclampsia included fewer than 3 of prenatal care visits, and age $\le$20 years. Protective factors were magnesium sulfate administration prior to seizure, history of abortions and longer gestational age. Having less than 3 prenatal care visits and being less than or equal to 20 years of age were predictors of eclampsia, whether of its development or progression from preeclampsia. Once preeclampsia is diagnosed, primigravid, diabetic, black, or obese women and those with urinary tract infections did not appear to exhibit any increased risk for the progression to eclampsia. The administration of magnesium sulfate was especially protective, followed by a positive history of abortions, 3 or more prenatal care visits, and longer gestational age. The protective effect of MgSO$\sb4$ was only slightly diminished when cases were restricted to the 65% who had a diagnosis of preeclampsia. The progression from preeclampsia to eclampsia may be largely preventable through adequate prenatal care and presumably the administration of magnesium sulfate. (Abstract shortened by UMI.) ^

Burden of invasive pneumococcal disease in Harris County, Texas (2003--2010) and the implication for enhanced public health surveillance of isolates

Invasive pneumococcal disease (IPD) causes significant health burden in the US, is responsible for the majority of bacterial meningitis, and causes more deaths than any other vaccine preventable bacterial disease in the US. The estimated National IPD rate is 14.3 cases per 100,000 population with a case-fatality rate of 1.5 cases per 100,000 population. Although cases of IPD are routinely reported to the local health department in Harris County Texas, the incidence (IR) and case-fatality (CFR) rates have not been reported. Additionally, it is important to know which serotypes of S. pneumoniae are circulating in Harris County Texas and to determine if ‘replacement disease’ is occurring. ^ This study reported incidence and case-fatality rates from 2003 to 2009, and described the trends in IPD, including the IPD serotypes circulating in Harris County Texas during the study period, particularly in 2008 and 2010. Annual incidence rates were calculated and reported for 2003 to 2009, using complete surveillance-year data. ^ Geographic information system (GIS) software was used to create a series of maps of the data reported during the study period. Cluster and outlier analysis and hot spot analysis were conducted using both case counts by census tract and disease rate by census tract. ^ IPD age- and race-adjusted IR for Harris County Texas and their 95% confidence intervals (CIs) were 1.40 (95% CI 1.0, 1.8), 1.71 (95% CI 1.24, 2.17), 3.13 (95% CI 2.48, 3.78), 3.08 (95% CI 2.43, 3.74), 5.61 (95% CI 4.79, 6.43), 8.11 (95% CI 7.11, 9.1), and 7.65 (95% CI 6.69, 8.61) for the years 2003 to 2009, respectively (rates were age- and race-adjusted to each year's midyear US population estimates). A Poisson regression model demonstrated a statistically significant increasing trend of about 32 percent per year in the IPD rates over the course of the study period. IPD age- and race-adjusted case-fatality rates (CFR) for Harris County Texas were also calculated and reported. A Poisson regression model demonstrated a statistically significant increasing trend of about 26 percent per year in the IPD case-fatality rates from 2003 through 2009. A logistic regression model associated the risk of dying from IPD to alcohol abuse (OR 4.69, 95% CI 2.57, 8.56) and to meningitis (OR 2.42, 95% CI 1.46, 4.03). ^ The prevalence of non-vaccine serotypes (NVT) among IPD cases with serotyped isolates was 98.2 percent. In 2008, the year with the sample more geographically representative of all areas of Harris County Texas, the prevalence was 96 percent. Given these findings, it is reasonable to conclude that ‘replacement disease’ is occurring in Harris County Texas, meaning that, the majority of IPD is caused by serotypes not included in the PCV7 vaccine. Also in conclusion, IPD rates increased during the study period in Harris County Texas.^

Magnetoencephalography as a putative biomarker for Alzheimer's disease.

Alzheimer’s Disease (AD) is the most common dementia in the elderly and is estimated to affect tens of millions of people worldwide. AD is believed to have a prodromal stage lasting ten or more years. While amyloid deposits, tau filaments, and loss of brain cells are characteristics of the disease, the loss of dendritic spines and of synapses predate such changes. Popular preclinical detection strategies mainly involve cerebrospinal fluid biomarkers, magnetic resonance imaging, metabolic PET scans, and amyloid imaging. One strategy missing from this list involves neurophysiological measures, which might be more sensitive to detect alterations in brain function. The Magnetoencephalography International Consortium of Alzheimer’s Disease arose out of the need to advance the use of Magnetoencephalography (MEG), as a tool in AD and pre-AD research. This paper presents a framework for using MEG in dementia research, and for short-term research priorities

Classical segmentation methods on novel MR imaging: a study of brain tissue segmentation of MP2RAGE vs MPRAGE

MP2RAGE has proven to be a bias-free MR acquisition with excellent contrast between grey and white matter. We investigated the ability of three state-of-the-art algorithms to automatically extract white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF) from MPRAGE and MP2RAGE images: unified Segmentation (S) in SPM82 , its extension New Segment (NS), and an in-house Expectation-Maximization Markov Random Field tissue classification3 (EM-MRF) with Graph Cut (GC) optimization4 . Our goal is to quantify the differences between MPRAGE and MP2RAGE-based brain tissue probability maps.

Extracellular HIV-1 virus protein R causes a large inward current and cell death in cultured hippocampal neurons: Implications for AIDS pathology

The small HIV-1 accessory protein Vpr (virus protein R) is a multifunctional protein that is present in the serum and cerebrospinal fluid of AIDS patients. We previously showed that Vpr can form cation-selective ion channels across planar lipid bilayers, introducing the possibility that, if incorporated into the membranes of living cells, Vpr might form ion channels and consequently perturb the maintained ionic gradient. In this study, we demonstrate, by a variety of approaches, that Vpr added extracellularly to intact cells does indeed form ion channels. We use confocal laser scanning microscopy to examine the subcellular localization of fluorescently labeled Vpr. Plasmalemma depolarization and damage are examined using the anionic potential-sensitive dye bis(1,3-dibutylbarbituric acid) trimethine oxonol and propidium iodide (PI), respectively, and the effect of Vpr on whole-cell current is demonstrated directly by using the patch-clamp technique. We show that recombinant purified extracellular Vpr associates with the plasmalemma of hippocampal neurons to cause a large inward cation current and depolarization of the plasmalemma, eventually resulting in cell death. Thus, we demonstrate a physiological action of extracellular Vpr and present its mechanistic basis. These findings may have important implications for neuropathologies in AIDS patients who possess significant amounts of Vpr in the cerebrospinal fluid.

Physiological response to long-term peripheral and central leptin infusion in lean and obese mice

Recent data have identified leptin as an afferent signal in a negative-feedback loop regulating the mass of the adipose tissue. High leptin levels are observed in obese humans and rodents, suggesting that, in some cases, obesity is the result of leptin insensitivity. This hypothesis was tested by comparing the response to peripherally and centrally administered leptin among lean and three obese strains of mice: diet-induced obese AKR/J, New Zealand Obese (NZO), and Ay. Subcutaneous leptin infusion to lean mice resulted in a dose-dependent loss of body weight at physiologic plasma levels. Chronic infusions of leptin intracerebroventricularly (i.c.v.) at doses of 3 ng/hr or greater resulted in complete depletion of visible adipose tissue, which was maintained throughout 30 days of continuous i.c.v. infusion. Direct measurement of energy balance indicated that leptin treatment did not increase total energy expenditure but prevented the decrease that follows reduced food intake. Diet-induced obese mice lost weight in response to peripheral leptin but were less sensitive than lean mice. NZO mice were unresponsive to peripheral leptin but were responsive to i.c.v. leptin. Ay mice did not respond to subcutaneous leptin and were 1/100 as sensitive to i.c.v. leptin. The decreased response to leptin in diet-induced obese, NZO, and Ay mice suggests that obesity in these strains is the result of leptin resistance. In NZO mice, leptin resistance may be the result of decreased transport of leptin into the cerebrospinal fluid, whereas in Ay mice, leptin resistance probably results from defects downstream of the leptin receptor in the hypothalamus.

The type 2 iodothyronine deiodinase is expressed primarily in glial cells in the neonatal rat brain

Thyroid hormone plays an essential role in mammalian brain maturation and function, in large part by regulating the expression of specific neuronal genes. In this tissue, the type 2 deiodinase (D2) appears to be essential for providing adequate levels of the active thyroid hormone 3,5,3′-triiodothyronine (T3) during the developmental period. We have studied the regional and cellular localization of D2 mRNA in the brain of 15-day-old neonatal rats. D2 is expressed in the cerebral cortex, olfactory bulb, hippocampus, caudate, thalamus, hypothalamus, and cerebellum and was absent from the white matter. At the cellular level, D2 is expressed predominantly, if not exclusively, in astrocytes and in the tanycytes lining the third ventricle and present in the median eminence. These results suggest a close metabolic coupling between subsets of glial cells and neurons, whereby thyroxine is taken up from the blood and/or cerebrospinal fluid by astrocytes and tanycytes, is deiodinated to T3, and then is released for utilization by neurons.