Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats

Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

Exploring eye movement analysis as a measure of selective visual attention in brain injured individuals

Primary Objective: To investigate the utility of using a new method of assessment for deficits in selective visual attention (SVA). Methods and Procedures: An independent groups design compared six participants with brain injuries with six participants from a non-brain injured control group. The Sensomotoric Instruments Eye Movement system with remote eye-tracking device (eye camera), and 2 sets of eight stimuli were employed to determine if the camera would be a sensitive discriminator of SVA in these groups. Main Outcomes and Results: The attention profile displayed by the brain injured group showed that they were slower, made more errors, were less accurate, and more indecisive than the control group. Conclusions: The utility of eye movement analysis as an assessment method was established, with implications for rehabilitation requiring further development. Key words: selective visual attention, eye movement analysis, brain injury

Effects of very low birthweight on brain structure in adulthood

Very-low-birthweight (VLBW) individuals are at high risk of brain injury in the perinatal period. We wished to determine how such early brain lesions affect brain structure in adulthood. Thirty-two VLBW adults (20 female, 12 male) and, 18 term, normal birthweight sibling control individuals (nine female, nine male) underwent structural MRI at a mean age of 23 years 4 months (range 17 to 33 years; SD 3.4). Images were analyzed using an automated tissue segmentation algorithm in order to estimate whole brain tissue class volumes in native space. Images were then warped to a template image in standard space. There was no significant between-group difference in whole brain, greymatter, white matter, or total cerebral spinal fluid (CSF) volumes. However, lateral ventricular volume was significantly increased by 41% in those with VLBW. The ratio of grey to white matter was also significantly increased (by 10%) in those with VLBW. Group comparison maps showed widespread changes in the distribution of grey and white matter, and relative excess of ventricular CSF, in the brains of VLBW individuals. Increased ventricular volume predicted decreased grey matter in subcortical nuclei and limbic cortical structures, and decreased periventricular white matter. We conclude that these diffuse abnormalities of grey and white matter are a consequence,of the interaction of perinatal brain injury and ongoing neurodevelopmental processes.

Procedural pain and brain development in premature newborns

Objective: Preterm infants are exposed to multiple painful procedures in the neonatal intensive care unit (NICU) during a period of rapid brain development. Our aim was to examine relationships between procedural pain in the NICU and early brain development in very preterm infants.

Methods: Infants born very preterm (N ¼ 86; 24–32 weeks gestational age) were followed prospectively from birth, and studied with magnetic resonance imaging, 3-dimensional magnetic resonance spectroscopic imaging, and diffusion tensor imaging: scan 1 early in life (median, 32.1 weeks) and scan 2 at term-equivalent age (median, 40 weeks). We calculated N-acetylaspartate to choline ratios (NAA/choline), lactate to choline ratios, average diffusivity, and white matter fractional anisotropy (FA) from up to 7 white and 4 subcortical gray matter regions of interest. Procedural pain was quantified as the number of skin-breaking events from birth to term or scan 2. Data were
analyzed using generalized estimating equation modeling adjusting for clinical confounders such as illness severity, morphine exposure, brain injury, and surgery.

Results: After comprehensively adjusting for multiple clinical factors, greater neonatal procedural pain was associated with reduced white matter FA (b ¼ 0.0002, p ¼ 0.028) and reduced subcortical gray matter NAA/choline (b ¼ 0.0006, p ¼ 0.004). Reduced FA was predicted by early pain (before scan 1), whereas lower NAA/choline was predicted by pain exposure throughout the neonatal course, suggesting a primary and early effect on subcortical structures with secondary white matter changes.

Interpretation: Early procedural pain in very preterm infants may contribute to impaired brain development.

The social consequences of mild head injury and executive dysfunction /

Mild head injury (MHI) is a serious cause of neurological impairment as is evident by the substantial percentage (15%) of individuals who remain symptomatic at least 1-year following "mild" head trauma. However, there is a paucity of research investigating the social consequences following a MHI. The first objective of this study was to examine whether measures of executive functioning were predictive of specific forms of antisocial behaviour, such as reactive aggression, impulsive antisocial behaviour, behavioural disinhibition, and deficits in social awareness after controlling for the variance accounted for by sex differences. The second objective was to investigate whether a history of MHI was predictive of these same social consequences after controlling for both sex differences and executive functioning. Ninety university students participated in neuropsychological testing and filled out self-report questionnaires. Fifty-two percent of the sample self-reported experiencing a MHI. As expected, men were more reactively aggressive and antisocial than women. Furthermore, executive dysfunction predicted reactive aggression and impulsive antisocial behaviour after controlling for sex differences. Finally, as expected, MHI status predicted reactive aggression, impulsive antisocial behaviour, and behavioural disinhibition after controlling for sex and executive fimctioning. MHI status and executive functioning did not predict social awareness or sensitivity to reward or punishment. These results suggest that incurring a MHI has serious social consequences that mirror the neurobehavioural profile following severe cases of brain injury. Therefore, the social sequelae after MHI imply a continuum of behavioural deficits between MHI and more severe forms of brain injury.

Electrophysiological and behavioural correlates of facial identity and expression perception deficits following a closed head injury /

A large variety of social signals, such as facial expression and body language, are conveyed in everyday interactions and an accurate perception and interpretation of these social cues is necessary in order for reciprocal social interactions to take place successfully and efficiently. The present study was conducted to determine whether impairments in social functioning that are commonly observed following a closed head injury, could at least be partially attributable to disruption in the ability to appreciate social cues. More specifically, an attempt was made to determine whether face processing deficits following a closed head injury (CHI) coincide with changes in electrophysiological responsivity to the presentation of facial stimuli. A number of event-related potentials (ERPs) that have been linked specifically to various aspects of visual processing were examined. These included the N170, an index of structural encoding ability, the N400, an index of the ability to detect differences in serially presented stimuli, and the Late Positivity (LP), an index of the sensitivity to affective content in visually-presented stimuli. Electrophysiological responses were recorded while participants with and without a closed head injury were presented with pairs of faces delivered in a rapid sequence and asked to compare them on the basis of whether they matched with respect to identity or emotion. Other behavioural measures of identity and emotion recognition were also employed, along with a small battery of standard neuropsychological tests used to determine general levels of cognitive impairment. Participants in the CHI group were impaired in a number of cognitive domains that are commonly affected following a brain injury. These impairments included reduced efficiency in various aspects of encoding verbal information into memory, general slower rate of information processing, decreased sensitivity to smell, and greater difficulty in the regulation of emotion and a limited awareness of this impairment. Impairments in face and emotion processing were clearly evident in the CHI group. However, despite these impairments in face processing, there were no significant differences between groups in the electrophysiological components examined. The only exception was a trend indicating delayed N170 peak latencies in the CHI group (p = .09), which may reflect inefficient structural encoding processes. In addition, group differences were noted in the region of the N100, thought to reflect very early selective attention. It is possible, then, that facial expression and identity processing deficits following CHI are secondary to (or exacerbated by) an underlying disruption of very early attentional processes. Alternately the difficulty may arise in the later cognitive stages involved in the interpretation of the relevant visual information. However, the present data do not allow these alternatives to be distinguished. Nonetheless, it was clearly evident that individuals with CHI are more likely than controls to make face processing errors, particularly for the more difficult to discriminate negative emotions. Those working with individuals who have sustained a head injury should be alerted to this potential source of social monitoring difficulties which is often observed as part of the sequelae following a CHI.

The Influence of Arousal on Moral Decision-making for Individuals with and without Mild Head Injury

Recent research has shown that University students with a history of self-reported mild head injury (MHI) are more willing to endorse moral transgressions associated with personal, relative to impersonal, dilemmas (Chiappetta & Good, 2008). However, the terms 'personal' and 'impersonal' in these dilemmas have functionally confounded the 'intentionality' of the transgression with the 'personal impact' or 'outcome' of the transgression. In this study we used a modified version of these moral dilemmas to investigate decision-making and sympathetic nervous system responsivity. Forty-eight University students (24 with MHI, 24 with no-MHI) read 24 scenarios depicting moral dilemmas varying as a function of 'intentionality' of the act (deliberate or unintentional) and its 'outcome' (physical harm, no physical harm, non-moral) and were required to rate their willingness to engage in the act. Physiological indices of arousal (e.g., heart rate - HR) were recorded throughout. Additionally, participants completed several neurocognitive tests. Results indicated significantly lowered HR activity at baseline, prior to, and during (but not after) making a decision for each type of dilemma for participants with MHI compared to their non-injured cohort. Further, they were more likely than their cohort to authorize personal injuries that were deliberately induced. MHI history was also associated with better performance on tasks of cognitive flexibility and attention; while students' complaints of postconcussive symptoms and their social problem solving abilities did not differ as a function of MHI history. The results provide subtle support for the hypothesis that both emotional and cognitive information guide moral decision making in ambiguous and emotionally distressing situations. Persons with even a MHI have diminished physiological arousal that may reflect disruption to the neural pathways of the VMPFC/OFC similar to those with more severe injuries.

Microstructural and metabolic changes in the brains of concussed athletes

Les commotions cérébrales ont longtemps été considérées comme une blessure ne comportant que peu ou pas de conséquences. Cependant, la mise à la retraite forcée de plusieurs athlètes de haut niveau, liée au fait d'avoir subi des commotions cérébrales multiples, a porté cette question au premier plan de la culture scientifique et sportive. Malgré la sensibilisation croissante du public et la compréhension scientifique accrue des commotions cérébrales, il reste encore beaucoup d’inconnus au sujet de ces blessures. En effet, il est difficile de comprendre comment cette atteinte peut avoir des effets si profonds malgré le fait qu’elle n’entraîne apparemment pas de conséquences physiques apparentes lorsque les techniques traditionnelles d’imagerie cérébrale sont utilisées. Les techniques de neuroimagerie fonctionnelle ont cependant contribué à répondre aux nombreuses questions entourant les conséquences des commotions cérébrales ainsi qu'à accroître la compréhension générale de la physiopathologie de commotions cérébrales. Bien que les techniques de base telles que l'imagerie structurelle comme les scans TC et IRM soient incapables de détecter des changements structurels dans la grande majorité des cas (Ellemberg, Henry, Macciocchi, Guskiewicz, & Broglio, 2009; Johnston, Ptito, Chankowsky, & Chen, 2001), d'autres techniques plus précises et plus sensibles ont été en mesure de détecter avec succès des changements dans le cerveau commotionné. Des études d’IRM fonctionelle ont entre autres établi une solide relation entre les altérations fonctionnelles et les symptômes post-commotionels (Chen, Johnston, Collie, McCrory, & Ptito, 2007; Chen et al., 2004; Chen, Johnston, Petrides, & Ptito, 2008; Fazio, Lovell, Pardini, & Collins, 2007). Les mesures électrophysiologiques telles que les potentiels évoqués cognitifs (ERP) (Gaetz, Goodman, & Weinberg, 2000; Gaetz & Weinberg, 2000; Theriault, De Beaumont, Gosselin, Filipinni, & Lassonde, 2009; Theriault, De Beaumont, Tremblay, Lassonde, & Jolicoeur, 2010) et la stimulation magnétique transcrânienne ou SMT (De Beaumont, Brisson, Lassonde, & Jolicoeur, 2007; De Beaumont, Lassonde, Leclerc, & Theoret, 2007; De Beaumont et al., 2009) ont systématiquement démontré des altérations fonctionnelles chez les athlètes commotionnés. Cependant, très peu de recherches ont tenté d'explorer davantage certaines conséquences spécifiques des commotions cérébrales, entre autres sur les plans structural et métabolique. La première étude de cette thèse a évalué les changements structurels chez les athlètes commotionnés à l’aide de l'imagerie en tenseur de diffusion (DTI) qui mesure la diffusion de l'eau dans la matière blanche, permettant ainsi de visualiser des altérations des fibres nerveuses. Nous avons comparé les athlètes commotionnés à des athlètes de contrôle non-commotionnés quelques jours après la commotion et de nouveau six mois plus tard. Nos résultats indiquent un patron constant de diffusion accrue le long des voies cortico-spinales et dans la partie du corps calleux reliant les régions motrices. De plus, ces changements étaient encore présents six mois après la commotion, ce qui suggère que les effets de la commotion cérébrale persistent bien après la phase aiguë. Les deuxième et troisième études ont employé la spectroscopie par résonance magnétique afin d'étudier les changements neurométaboliques qui se produisent dans le cerveau commotionné. La première de ces études a évalué les changements neurométaboliques, les aspects neuropsychologiques, et la symptomatologie dans la phase aiguë post-commotion. Bien que les tests neuropsychologiques aient été incapables de démontrer des différences entre les athlètes commotionnés et non-commotionnés, des altérations neurométaboliques ont été notées dans le cortex préfrontal dorsolatéral ainsi que dans le cortex moteur primaire, lesquelles se sont avérées corréler avec les symptômes rapportés. La deuxième de ces études a comparé les changements neurométaboliques immédiatement après une commotion cérébrale et de nouveau six mois après l’atteinte. Les résultats ont démontré des altérations dans le cortex préfrontal dorsolatéral et moteur primaire dans la phase aiguë post-traumatique, mais seules les altérations du cortex moteur primaire ont persisté six mois après la commotion. Ces résultats indiquent que les commotions cérébrales peuvent affecter les propriétés physiques du cerveau, spécialement au niveau moteur. Il importe donc de mener davantage de recherches afin de mieux caractériser les effets moteurs des commotions cérébrales sur le plan fonctionnel.

Cannabidiol-treated Rats Exhibited Higher Motor Score After Cryogenic Spinal Cord Injury

Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.

Impact of traumatic dental injuries and malocclusions on quality of life of young children

Abstract Background The presence of traumatic dental injuries and malocclusions can have a negative impact on quality of life of young children and their parents, affecting their oral health and well-being. The aim of this study was to assess the impact of traumatic dental injuries and anterior malocclusion traits on the Oral Health-Related Quality of Life (OHRQoL) of children between 2 and 5 years-old. Methods Parents of 260 children answered the six domains of the Early Childhood Oral Health Impact Scale (ECOHIS) on their perception of the OHRQoL (outcome). Two calibrated dentists assessed the types of traumatic dental injuries (Kappa = 0.9) and the presence of anterior malocclusion traits (Kappa = 1.0). OHRQoL was measured using the ECOHIS. Poisson regression was used to associate the type of traumatic dental injury and the presence of anterior malocclusion traits to the outcome. Results The presence of anterior malocclusion traits did not show a negative impact on the overall OHRQoL mean or in each domain. Only complicated traumatic dental injuries showed a negative impact on the symptoms (p = 0.005), psychological (p = 0.029), self image/social interaction (p = 0.004) and family function (p = 0.018) domains and on the overall OHRQoL mean score (p = 0.002). The presence of complicated traumatic dental injuries showed an increased negative impact on the children's quality of life (RR = 1.89; 95% CI = 1.36, 2.63; p < 0.001). Conclusions Complicated traumatic dental injuries have a negative impact on the OHRQoL of preschool children and their parents, but anterior malocclusion traits do not.

Adjunctive daptomycin attenuates brain damage and hearing loss more efficiently than rifampin in infant rat pneumococcal meningitis

Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model. Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (P < 0.01) less apoptosis, and significantly (P < 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.

Manipulation of antioxidant pathways in neonatal murine brain

To assess the role of brain antioxidant capacity in the pathogenesis of neonatal hypoxic-ischemic brain injury, we measured the activity of glutathione peroxidase (GPX) in both human-superoxide dismutase-1 (hSOD1) and human-GPX1 overexpressing transgenic (Tg) mice after neonatal hypoxia-ischemia (HI). We have previously shown that mice that overexpress the hSOD1 gene are more injured than their wild-type (WT) littermates after HI, and that H(2)O(2) accumulates in HI hSOD1-Tg hippocampus. We hypothesized that lower GPX activity is responsible for the accumulation of H(2)O(2). Therefore, increasing the activity of this enzyme through gene manipulation should be protective. We show that brains of hGPX1-Tg mice, in contrast to those of hSOD-Tg, have less injury after HI than WT littermates: hGPX1-Tg, median injury score = 8 (range, 0-24) versus WT, median injury score = 17 (range, 2-24), p < 0.01. GPX activity in hSOD1-Tg mice, 2 h and 24 h after HI, showed a delayed and bilateral decline in the cortex 24 h after HI (36.0 +/- 1.2 U/mg in naive hSOD1-Tg versus 29.1 +/- 1.7 U/mg in HI cortex and 29.2 +/- 2.0 for hypoxic cortex, p < 0.006). On the other hand, GPX activity in hGPX1-Tg after HI showed a significant increase by 24 h in the cortex ipsilateral to the injury (48.5 +/- 5.2 U/mg, compared with 37.2 +/- 1.5 U/mg in naive hGPX1-Tg cortex, p < 0.008). These findings support the hypothesis that the immature brain has limited GPX activity and is more susceptible to oxidative damage and may explain the paradoxical effect seen in ischemic neonatal brain when SOD1 is overexpressed.

An infant mouse model of brain damage in pneumococcal meningitis

Bacterial meningitis due to Streptococcus pneumoniae is associated with an significant mortality rate and persisting neurologic sequelae including sensory-motor deficits, seizures, and impairments of learning and memory. The histomorphological correlate of these sequelae is a pattern of brain damage characterized by necrotic tissue damage in the cerebral cortex and apoptosis of neurons in the hippocampal dentate gyrus. Different animal models of pneumococcal meningitis have been developed to study the pathogenesis of the disease. To date, the infant rat model is unique in mimicking both forms of brain damage documented in the human disease. In the present study, we established an infant mouse model of pneumococcal meningitis. Eleven-days-old C57BL/6 (n = 299), CD1 (n = 42) and BALB/c (n = 14) mice were infected by intracisternal injection of live Streptococcus pneumoniae. Sixteen hours after infection, all mice developed meningitis as documented by positive bacterial cultures of the cerebrospinal fluid. Sixty percent of infected C57BL/6 mice survived more than 40 h after infection (50% of CD1, 0% of BALB/c). Histological evaluations of brain sections revealed apoptosis in the dentate gyrus of the hippocampus in 27% of infected C57BL/6 and in 5% of infected CD1 mice. Apoptosis was confirmed by immunoassaying for active caspase-3 and by TUNEL staining. Other forms of brain damage were found exclusively in C57BL/6, i.e. caspase-3 independent (pyknotic) cell death in the dentate gyrus in 2% and cortical damage in 11% of infected mice. This model may prove useful for studies on the pathogenesis of brain injury in childhood bacterial meningitis.

Erythropoietin neuroprotection is enhanced by direct cortical application following subdural blood evacuation in a rat model of acute subdural hematoma

Recombinant human erythropoietin (EPO) has been successfully tested as neuroprotectant in brain injury models. The first large clinical trial with stroke patients, however, revealed negative results. Reasons are manifold and may include side-effects such as thrombotic complications or interactions with other medication, EPO concentration, penetration of the blood-brain-barrier and/or route of application. The latter is restricted to systemic application. Here we hypothesize that EPO is neuroprotective in a rat model of acute subdural hemorrhage (ASDH) and that direct cortical application is a feasible route of application in this injury type. The subdural hematoma was surgically evacuated and EPO was applied directly onto the surface of the brain. We injected NaCl, 200, 2000 or 20,000IU EPO per rat i.v. at 15min post-ASDH (400μl autologous venous blood) or NaCl, 0.02, 0.2 or 2IU per rat onto the cortical surface after removal of the subdurally infused blood t at 70min post-ASDH. Arterial blood pressure (MAP), blood chemistry, intracranial pressure (ICP), cerebral blood flow (CBF) and brain tissue oxygen (ptiO2) were assessed during the first hour and lesion volume at 2days after ASDH. EPO 20,000IU/rat (i.v.) elevated ICP significantly. EPO at 200 and 2000IU reduced lesion volume from 38.2±0.6mm(3) (NaCl-treated group) to 28.5±0.9 and 22.2±1.3mm(3) (all p<0.05 vs. NaCl). Cortical application of 0.02IU EPO after ASDH evacuation reduced injury from 36.0±5.2 to 11.2±2.1mm(3) (p=0.007), whereas 0.2IU had no effect (38.0±9.0mm(3)). The highest dose of both application routes (i.v. 20,000IU; cortical 2IU) enlarged the ASDH-induced damage significantly to 46.5±1.7 and 67.9±10.4mm(3) (all p<0.05 vs. NaCl). In order to test whether Tween-20, a solvent of EPO formulation 'NeoRecomon®' was responsible for adverse effects two groups were treated with NaCl or Tween-20 after the evacuation of ASDH, but no difference in lesion volume was detected. In conclusion, EPO is neuroprotective in a model of ASDH in rats and was most efficacious at a very low dose in combination with subdural blood removal. High systemic and topically applied concentrations caused adverse effects on lesion size which were partially due to increased ICP. Thus, patients with traumatic ASDH could be treated with cortically applied EPO but with caution concerning concentration.

Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis.

BackgroundApproximately 7% of survivors from meningococcal meningitis (MM) suffer from neurological sequelae due to brain damage in the course of meningitis. The present study focuses on the role of matrix metalloproteinases (MMPs) in a novel mouse model of MM-induced brain damage.MethodsThe model is based on intracisternal infection of BALB/c mice with a serogroup C Neisseria meningitidis strain. Mice were infected with meningococci and randomised for treatment with the MMP inhibitor batimastat (BB-94) or vehicle. Animal survival, brain injury and host-response biomarkers were assessed 48 h after meningococcal challenge.ResultsMice that received BB-94 presented significantly diminished MMP-9 levels (p¿<¿0.01), intracerebral bleeding (p¿<¿0.01), and blood-brain barrier (BBB) breakdown (p¿<¿0.05) in comparison with untreated animals. In mice suffering from MM, the amount of MMP-9 measured by zymography significantly correlated with both intracerebral haemorrhage (p¿<¿0.01) and BBB disruption (p¿<¿0.05).ConclusionsMMPs significantly contribute to brain damage associated with experimental MM. Inhibition of MMPs reduces intracranial complications in mice suffering from MM, representing a potential adjuvant strategy in MM post-infection sequelae.