Objective neuropsychological deficits in post-traumatic stress disorder and mild traumatic brain injury: what remains beyond symptom similarity?

This exploratory study intends to characterize the neuropsychological profile in persons with post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) using objective measures of cognitive performance. A neuropsychological battery of tests for attention, memory and executive functions was administered to four groups: PTSD (n = 25), mTBI (n = 19), subjects with two formal diagnoses: Post-traumatic Stress Disorder and Mild Traumatic Brain Injury (mTBI/PTSD) (n = 6) and controls (n = 25). Confounding variables, such as medical, developmental or neurological antecedents, were controlled and measures of co-morbid conditions, such as depression and anxiety, were considered. The PTSD and mTBI/PTSD groups reported more anxiety and depressive symptoms. They also presented more cognitive deficits than the mTBI group. Since the two PTSD groups differ in severity of PTSD symptoms but not in severity of depression and anxiety symptoms, the PTSD condition could not be considered as the unique factor affecting the results. The findings underline the importance of controlling for confounding medical and psychological co-morbidities in the evaluation and treatment of PTSD populations, especially when a concomitant mTBI is also suspected.

A study of sexuality following traumatic brain injury : moving towards the validation of a biopsychosocial model

L’étude de la sexualité dans le contexte des maladies neurologiques est un domaine émergent qui nous permet de mieux comprendre les corrélats cérébraux et neurocomportementaux de divers aspects de la sexualité. Les changements au sujet de la sexualité sont fréquents à la suite de troubles neurologiques tels que les blessures de la moelle épinière, la sclérose en plaques, l’accident vasculaire cérébral, l'épilepsie et les traumatismes craniocérébraux (TCC). Compte tenu de la complexité de la sexualité après un TCC, celle-ci doit être analysée à partir d'une perspective biopsychosociale qui comprend trois facteurs interdépendants : a) les facteurs neuropsychologiques et psychologiques, b) les variables médicales et physiques, et c) les facteurs relationnels. L’objectif de cette thèse était d’étudier certains éléments de la sexualité auprès de personnes ayant subi un TCC afin de fournir des preuves empiriques pour contribuer à la validation d’une perspective biopsychosociale de la sexualité après un TCC. Trois études quantitatives originales ont été effectuées auprès de personnes ayant subi un TCC léger, modéré ou grave et ayant reçu des services de réadaptation post-TCC, et d’un groupe de témoins en bonne santé, tous vivant dans la communauté. Les groupes étaient comparables en ce qui concerne l’âge, le sexe, le nombre d’années de scolarité, le statut d’emploi et relationnel, et le revenu annuel. Les variables ciblant la sexualité, incluses dans cette thèse, étaient la qualité de vie sexuelle, le comportement sexuel à risque, et la sociosexualité (p. ex., les différences individuelles en ce qui concerne la volonté d’une personne à avoir des relations sexuelles sans engagement). Les variables neuropsychologiques et psychologiques incluaient les fonctions exécutives, la dépression et l’anxiété. Les aspects médicaux et physiques englobaient les symptômes postcommotionnels. Les facteurs relationnels comprenaient les attitudes envers l'infidélité. Les résultats démontrent que par rapport aux témoins en santé, les individus avec un TCC ont montré une diminution de la qualité de vie sexuelle, alors que les groupes étaient comparables sur le plan du comportement sexuel à risque, de la sociosexualité et des attitudes envers l'infidélité. Par ailleurs, les résultats ont montré une différence entre les hommes et les femmes sur le plan de la sociosexualité (p. ex., plus restrictive chez la femme). Chez les personnes ayant subi un TCC, une faible qualité de vie sexuelle était significativement associée à un nombre élevé de symptômes postcommotionnels, un comportement sexuel plus à risque corrélait avec une plus grande fréquence de symptômes dysexécutifs, et une plus faible acceptation de l'infidélité était liée à une sociosexualité moins restrictive. Les résultats de ces trois études soutiennent une perspective biopsychosociale de la sexualité après le TCC. Elles apportent des connaissances nouvelles en ce qui a trait aux domaines de la sexualité qui peuvent être touchés après un TCC, ainsi qu’à certaines variables neuropsychologiques et psychologiques, médicales et physiques, et relationnelles qui sont associées à ces changements. Les implications théoriques, ainsi que pour la pratique clinique et la réadaptation sont discutées. Les limitations des études sont présentées et des recommandations pour la recherche sont proposées. Le modèle biopsychosocial peut être utilisé comme une référence pour guider la recherche future dans ce domaine. D’autres études sur la sexualité et le développement d'interventions multidisciplinaires dans ce domaine pour les personnes TCC sont nécessaires.

Metabolomics analysis in rats with thiamine deficiency identifies key metabolites in vulnerable brain regions and suggests neural stem progenitor cells play a role in ameliorating metabolic dysfunction

La documentation scientifique fait état de la présence, chez l’adulte, de cellules souches et progénitrices neurales (CSPN) endogènes dans les zones sous-ventriculaire et sous-granulaire du cerveau ainsi que dans le gyrus denté de l’hippocampe. De plus, un postulat selon lequel il serait également possible de retrouver ce type de cellules dans la moelle épinière et le néocortex des mammifères adultes a été énoncé. L’encéphalopathie de Wernicke, un trouble neurologique grave toutefois réversible qui entraîne un dysfonctionnement, voire une défaillance du cerveau, est causée principalement par une carence importante en thiamine (CT). Des observations récentes laissent envisager que les facteurs en cause dans la prolifération et la différenciation des CSPN pourraient également jouer un rôle important lors d’un épisode de CT. L’hypothèse, selon laquelle l’identification de nouveaux métabolites entrant dans le mécanisme ou la séquence de réactions se soldant en une CT pourraient en faciliter la compréhension, a été émise au moyen d'une démarche en cours permettant d’établir le profil des modifications métaboliques qui surviennent en de telles situations. Cette approche a été utilisée pour constater les changements métaboliques survenus au niveau du foyer cérébral dans un modèle de rats déficients en thiamine (rats DT), particulièrement au niveau du thalamus et du colliculus inférieur (CI). La greffe de CSPN a quant à elle été envisagée afin d’apporter de nouvelles informations sur la participation des CSPN lors d’un épisode de CT et de déterminer les bénéfices thérapeutiques potentiels offerts par cette intervention. Les sujets de l’étude étaient répartis en quatre groupes expérimentaux : un premier groupe constitué de rats dont la CT était induite par la pyrithiamine (rats DTiP), un deuxième groupe constitué de rats-contrôles nourris ensemble (« pair-fed control rats » ou rats PFC) ainsi que deux groupes de rats ayant subi une greffe de CSPN, soit un groupe de rats DTiP greffés et un dernier groupe constitué de rats-contrôles (rats PFC) greffés. Les échantillons de foyers cérébraux (thalamus et CI) des quatre groupes de rats ont été prélevés et soumis à des analyses métabolomiques non ciblées ainsi qu’à une analyse visuelle par microscopie à balayage électronique (SEM). Une variété de métabolites-clés a été observée chez les groupes de rats déficients en thiamine (rats DTiP) en plus de plusieurs métabolites dont la documentation ne faisait pas mention. On a notamment constaté la présence d’acides biliaires, d’acide cynurénique et d’acide 1,9— diméthylurique dans le thalamus, alors que la présence de taurine et de carnosine a été observée dans le colliculus inférieur. L’étude a de plus démontré une possible implication des CSPN endogènes dans les foyers cérébraux du thalamus et du colliculus inférieur en identifiant les métabolites-clés ciblant les CSPN. Enfin, les analyses par SEM ont montré une amélioration notable des tissus à la suite de la greffe de CSPN. Ces constatations suggèrent que l’utilisation de CSPN pourrait s’avérer une avenue thérapeutique intéressante pour soulager la dégénérescence symptomatique liée à une grave carence en thiamine chez l’humain.

Decreased 5-HT2C receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats

The purpose of this study was to investigate the role of central 5-HT2C receptor binding in rat model of pancreatic regeneration using 60-70% pancreatectomy. The 5-HT and 5-HT2c receptor kinetics were studied in cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [3H] mesulergine in cerebral cortex showed a significant decrease (p < 0.05) in maximal binding (B^,ax) without any change in Kd in 72 h pancreatectomised rats compared with sham. The decreased Bmax reversed to sham level by 7 days after pancreatectomy. In brain stem , Scatchard analysis showed a significant decrease (p < 0.01) in Bax with a significant increase (p < 0.01) in Kd. Competition analysis in brain stem showed a shift in affinity towards a low affinity. These parameters were reversed to sham level by 7 days after pancreatectomy. Thus the results suggest that 5-HT through the 5-HT2C receptor in the brain has a functional regulatory role in the pancreatic regeneration. (Mol Cell Biochem 272: 165-170, 2005)

Decreased 5-F{T1fti Receor Gene Expression and 5-F4T11 Receptor Protein in the Cerebra'' Cortex and Brain Stem during Pancreatic Regenera tion in Rats

The present study was to investigate the rote of central 5-11T and 5-HT,:v receptor Lindin4o and acne expression in it 'at mo(lel of pancreatic regeneration using 60" -, pancreatcutumy. The pancreatic regeneration was evaluated by 5-HT content and 5-HT,,receptor gene expression in the cerebral cortex (CC) and brain stem MS) of Alain opcrate,t, 7 It utd 7 (.lays panereatectomised rats. 5-11T content significantly increased in the CC' (I' 1.1)11 and 13S (P 0.05) of 72 Ii p.ntcreateetomiscd rats. Sympathetic activity was decreased as indicated by the significantly decreased norcpiuephrine (NIi) and epinephrine (FTI) Icvcl (1' < 0.001 and P < 0.05) in the plasma of 72 h panereateetomised rats. 5-111 ,^, receptor density and affinity was decreased in the CC (P < 0.01) and BS (P < 0.01). These rh:)nge; correlated with a diminished 5-IITIA receptor mRNA expression in the brain region. studied. Our resuils suggest that the brain 5-11T through 5-HTin receptor has it funcuon:0 rule iii 11w pi+ncreatic regcner:ttion through the sympathetic regulation.

Enhanced /3-adrenergic receptors in the brain and pancreas during pancreatic regeneration in weanling rats

Adrenergic stimulation has an inyortant role in the pancreatic It-cell proliferation and insulin secretion. In the present study. we have investigaled how sympathetic system mgulales the panrrealic n I rnerui nr ht an:ilyiing I'pinephi inn 1111 ), Norepinephrinc (NE) and /1-adrenergic receptor changes in the brain as (%eli is in the I swirls. Fill and NII showed a significant decrease in the brain regions, pancreas and plasma :rt 72Ius iller partial prurcrealectonty. We observed an increase in the circulating insulin levels at 72 hrs. Scatchard analysis using I CHI propranolol showed a significant increase in the number of loth the low affinity and high affinity t-adrenergic receplors in cerebral cortex and hypothalamus of partially pancreatectornised rats during peak DNA synthesis. The affinity of the receptors decrea,ed significantly in the low and high affinity receptors of cerebral cortex and the high affinity hypothalamic receptors. In file brain stein, low affinity receptors were increased significantly during regeneration whereas there was no change in the high affinity receptors. The pancreatic ff-adrenergic receptors were also up regulated at 72 firs after partial panerealectony. In vitro studies showed that /i-adrenergic receptors are positive regulators of islet cell proliferation and insulin secretion. Thus our results suggest that the t-adrenergic receptors are functionally enhanced during pancreatic regeneration, which in turn increases pancreatic ft-cell proliferation an(hilisulin secretion in wean hug rats.

Decreased a2-adrenergic receptor in the brain stem and pancreatic islets during pancreatic regeneration in weanling rats

Sympathetic stimulation inhibits insulin secretion. a2-Adrenergic receptor is known to have a regulatory role in the sympathetic function. We investigated the changes in the a2-adrenergic receptors in the brain stein and pancreatic islets using [3H]Yohimbine during pancreatic regeneration in weanling rats. Brain stem and pancreatic islets of experimental rats showed a significant decrease (p<0.001) in norepinephrine (NE) content at 72 h after partial pancreatectomy. The epinephrine (EPI) content showed a significant decrease (p<0.001) in pancreatic islets while it was not detected in brain stem at 72 h after partial pancreatectomy. Scatchard analysis of [3H]Yohimbine showed a significant decrease (p<0.05) and Kd at 72 h after partial pancreatectomy in the brain stem. In the pancreatic islets, Scatchard analysis of [3H]Yohimbine showed a signiinfiBca'nnatx decrease (p<0.001) in B,nax and Kd (p<0.05) at 72 h after partial pancreatectomy. The binding parameters reversed to near sham by 7 days after pancreatectomy both in brain stein and pancreatic islets. This shows that pancreatic insulin secretion is influenced by central nervous system inputs from the brain stem. In vitro studies with yohimbine showed that the a2-adrenergic receptors are inhibitory to islet DNA synthesis and insulin secretion. Thus our results suggest that decreased a2-adrenergic receptors during pancreatic regeneration functionally regulate insulin secretion and pancreatic 13-cell proliferation in weanling rats.

Decreased (x1-Adrenergic Receptor Binding in the Cerebral Cortex and Brain Stem during Pancreatic Regeneration in Rats

purpose of this study was to investigate the role of brain al-adrenergic receptor binding in the rat model of pancreatic regeneration using 60-70% pancre:dectorny. The a, -adrenergic receptors kinetics was studied in the cerebral cor:cx and brain stem of sham operated . 72 It pan- crea(ectoinised and 7 days pancreatectomised rats. Scar chard analysis with I `I I lprazocin in cerebral cartes and brain stein showed a significant decrease (/' < 0.01). (P < 0.05) in maximal binding ( 1),,,,,) with it significant decrease (P < 0.001 ), ( P < 0.01) in the K,,in 72 It pancreatecto- raised rats compared with sham , respectively . Competition analysis in cerebral cortex and brain stem showed it shift in affinity during pancreatic regeneration . The sympathetic activity was decreased as indicated by the significantly de- increased norepinephrine level in the plasma (P < 0.001), cerebral cortex (P < 0.01) and brain stem (P < 0.001) of 72 h pancreatectomised rats compared to sham . Thus, from our results it is suggested that the central a, -adrenergic receptors have a functional role in the pancreatic regenera- Lion mediated through the sympathetic pathway.

Alterations in the muscarinic M I and M3 receptor gene expression in the brain stem during pancreatic regeneration and insulin secretion in weanling rats

Muscarinic M1 and M3 receptor changes in the brain stem during pancreatic regeneration were investigated. Brain stem acetylcholine esterase activity decreased at the time of regeneration . Sympathetic activity also decreased as indicated by the norepinephrine (NE) and epinephrine (EPI) content of adrenals and also in the plasma. Muscarinic Ml and M3 receptors showed reciprocal changes in the brain stem during regeneration. Muscairnic M1 receptor number decreased at time of regeneration without any change in the affinity. High affinity M3 receptors showed an increase in the number. The affinity did not show any change . The number of low affinity receptors decreased with decreased Kd at 72 hours after partial pancreatectomy. The Kd reversed to control value with a reversal of the number of receptors to near control value . Gene expression studies also showed a similar change in the mRNA level of Ml and M3 receptors . These alterations in the muscarinic receptors regulate sympathetic activity and maintain glucose level during pancreatic regeneration. Central muscarinic M1 and M3 receptor subtypes functional balance is suggested to regulate sympathetic and parasympathetic activity, which in turn control the islet cell proliferation and glucose homeostasis.

Increased 5-HT2C Receptor Binding in the Brain Stem And Cerebral Cortex During Liver Regeneration And Hepatic Neoplasia In Rats

In the present study, serotonin 2C (5-HT2c) receptor binding parameters in the brainstem and cerebral cortex were investigated during liver generation after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatic neoplasia in male Wistar rats. The serotonin content increased significantly (p<0.01) in the cerebral cortex after PH and in NDEA induced hepatic neoplasia. Brain stem serotonin content increased significantly (p<0.05) after PH and (p<0.001) in NDEA induced hepatic neoplasia. The number and affinity of the 5-HT2c receptors in the crude synaptic membrane preparations of the brain stem showed a significant (p<0.001) increase after PH and in NDEA induced hepatic neoplasia. The number and affinity of 5-HT2c receptors increased significantly (p<0.001) in NDEA induced hepatic neoplasia in the crude synaptic membrane preparations of the cerebral cortex. There was a significant (p<0.01) increase in plasma norepinephrine in PH and (p<0.001) in NDEA induced hepatic neoplasia, indicating sympathetic stimulation. Thus, our results suggest that during active hepatocyte proliferation 5-HT2c receptor in the brain stem and cerebral cortex are up-regulated which in turn induce hepatocyte proliferation mediated through sympathetic stimulation.

Polyunsaturated Fatty Acids (PUFA) Regulate Neurotransmitter Contents in Rat Brain

The effects of feeding of 6-propyllhiouracil (6-I'fU) and potyunsaturatcd fatty acids (I'UFA) independently and ill combination and administration (ip) of a single close of Iriiodothyronine (I',) (2.51ig/IOOg body wl) along with feeding of 6- PTU and PUFA were studied in cal brain. Dopamine (DA), 5-hydroxytryplophan (5-IIl'I'), serolouin (5-Ill), 5-hydioxy indole acetic acid (5-111AA), norepinephrine (NF) :uul ceinephrinn (I?I'l) contenls were assayed in the hypothalannls and ccrc bral cortex regions. It was found that 6-P"l'U Iccding resulted in decrease in dopamine, 5-III', 5 II I I' and 5 IIiAA in both regions. In animals fed wills PUFA followed by adnliuislralion of T,. the I)A level was found normal.

Decreased GyBAA Receptor Function in the Brain Stem during Pancreatic Regeneration in Rats

Gamma amino outyric acid is a major inhibitory neurotrarsr titter in the central nervous system. In the preset study sv, Have investigate(' the alteration of GABA receptor, In t he hrain stem of rats during pancreatic regeneration. Three groups of rats were used for the study: sham operated, 72 It and 7 days partially pancreatectonnsea. GABA was (juan- (ified by [H]GABA receptor iispiacement method. GABA receptor kin: 10, pat at i et•ers were studied by using the binding of F'.](iAhA as ligand to the Triton X-100 treated me,i1,;-:mes a1,J displacement with unlabelled GABA. GhRA,v receptor activity was studied by using the [` -1 h3cuculline and displacement with unlabellecV euculline. ;.\13A content significantly decreased (1' < (1.(101 ) it, 0-e brain stern during the regeneration of pancreas. 'I hl, high affinity (IAI3A receptor binding sho?:ed it sigii'f cant decrease in 131„.,\ (P < 11.01) and K,I 1).05) n 72 h and 7 days after partial pancreatee 'timv. ";:flhicuculline hin(Iing showed it signih eat, 'le ( r(, :,e in /Jn1,s and K,I (P < 0.001) in 72 h pa^.rcreaw,, mised rats when compared with sham wt--tt' as P,n and K,I reversed to near sham after 7 da,s of pancreatectomv. The results sugge,) that GAB A throur,r; ('GABA receptors in brain Atcem has a regulatory uie during active regeneration of pancreas which will have inunense clinical significance in the treatment of cliahetcs.

ALPHA2 Adrenergic and High Affinity Serotonergic Receptor Changes in the Brain Stem of Streptozotocin induced Diabetic Rats

The brain stems (13S) of streptozotocin (STZ)-diabetic rats were studied lo see the changes in neurotransmitter content and their receptor regulation. The norepinephrine (NE) content determined in the diabetic brain stems did ^ control. an E showed la while PI turnover hri content increased significantly compared N^r eNveFa o the recep significant increase. The alpha2 adrenergic receptor IneP utisoulinntreat d ratsetheNE contentt dec^ sled was significantly reduced during diabetes. in versedcto reanorm sed ulcrea e tK reatment the state. while EPI content remained increased as in die diabetic B,, for a]pha2 adrenergic receptors slw^nificantly while Unlabelled clonidine inhibited [31-I]NE binding in BS of control, diabetic and insulin treated ulations bindi diabetic rats showed that alpha2 adrenergicre^ punks cojnidiabetic animal the ligand bound sites with Hill slopes significantly away from unity. weaker to the low affinity site than in controls. Insulin treatment reversed[ this allumbmn to control levels. The displacement analysis using (-)-epinephrine age in control and diabetic animals revealed two populations of receptor affinidtyo=tat ss. In control animals, when GTP analogue added with epinephrine, the curve nagnlde caofnfitnroit yS model; but in the diabetic BS this effect `not aobserved. In bintact oth the diabetic data thus showlthat the effects of monovalent cations on affinity alphaz adrenergic receptors have a reduced affinity v due in stem ialtered Itscppeomson(5- regulation. The serotonin (5-HT) coat hydroxy) tryptophan (5-HTP) showed an increase and its breakdown metabolite (5-hydroxy) indoleacetic acid (5-I{IAA) showed a significant decrease. This showed that in serotonergic which l nerves there is a disturbance in both synthetic and breankduomwnbers pretma'med ana increased 5-HT. The high affinity serotonin receptor um ese serotonerg decrease in the receptor affinity. The insulin ^treatmentsturtiy showsha decreased serotonergic receptor kinetic parameters to control level. receptor function. These changes in adrenergic and serotonergic receptor function were suggested to be important in insulin function during STZ diabetes.

Age-Dependent Properties of Acid & Alkaline DNases in Chick Brain

Acid and alkaline DNase activities in partially purified preparations from young and old chick brain were measured. The specific activity of acid DNase from old brain was lower by about 50% than that of enzyme from young brain , whereas alkaline DNase exhibited only marginal difference in activity of the two preparations . Study of various properties, viz. heat-stability and effect of exogenous compounds like Mg=', Hgl', Zn=', PHM B , on these enzymes revealed that while acid DNase in old brain is more susceptible to heat and heavy metal ion inhibition , alkaline DNase is devoid of any age-dependent variation in its properties.