Medulla Pons Research Articles

Pentylenetetrazole-Induced Seizures in Wistar Male Albino Rats with Reference to Glutamate Metabolism.

Epilepsy is a common and heterogenous neurological disorder characterized by recurrent spontaneous seizures. Animal models like rats play a crucial role in finding of mechanism of epilepsy in different brain regions. i.e., cerebral cortex, cerebellum, hippocampus, and pons medulla. Glutamate is an important excitatory neurotransmitter in the central nervous system and also glutamate plays a vital role in neuronal development and memory. The process of neuronal death evolved by glutamate receptor activation, has been hypothesized in both acute and chronic degenerative disorders including epilepsy. Considering the multifactorial neurochemical and neurophysiological malfunctions consequent to epileptic seizures, a few antiepileptic drugs are designed, to mitigate the debilitating aspects of epilepsy. Rat model, pentylenetetrazole (PTZ), an anticonvulsant drug, was selected for the present study. Induction of epilepsy/convulsions was induced by an intraperitoneal injection of PTZ (60 mg/kg body weight) in saline. Biochemical assays performed through spectrophotometer. Glutamine and Glutamine synthetase levels were decreased in the epileptic rats brain regions i.e., hippocampus, cerebellum, cerebral cortex, and pons medulla; glutamate dehydrogenase and glutaminase levels were increased in all the regions of epilepsy induced rats. Highest values are recorded in hippocampus when compared to other brain regions. PTZ suppresses the function of Glutamine and Glutamine synthetase activities in selected brain regions of rat and enhances the activities of the glutaminase and glutamate dehydrogenase when compared to control rats.

Effect of Pimpinella tirupatiensis Extract on Brain Free Radical Toxicity in STZ Induced Diabetic Rats

The objective of this study was to investigate the effects of Pimpinella tirupatiensis on oxidative stress markers in different regions of the brain (cerebral cortex, cerebellum, hippocampus, and Pons medulla) in rats with diabetes. Diabetes was induced in wistar rats by injecting them with STZ (40 mg/kg). The rats were then administered Pimpinella tirupatiensis aqueous extract (750 mg/kg / b.w. /day) and glibenclamide (Glb) (20 mg/ kg / b.w. /day) orally for 30 days. After 4 weeks of high blood sugar, the activity of antioxidant enzymes was measured in both the diabetic and control groups. Diabetes can worsen nerve damage and cause oxidative damage due to high blood sugar levels. The diabetic rats displayed a significant decrease in levels of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) and reduced glutathione. However, when ginger was administered orally, it enhanced the activity of antioxidant enzymes in the diabetic rats. This suggests that Pimpinella tirupatiensis has a protective effect on the brain by enhancing antioxidant defense mechanisms in diabetic rats. Furthermore, it has a neuroprotective effect by enhancing the brain's antioxidant defense mechanisms and thereby attenuating the progression of hyperglycemia and some complications caused by diabetes in the rat brain.

Characterization of the biochemical and behavioral effects of cannabidiol: implications for migraine

Cannabidiol (CBD) is the main pharmacologically active phytocannabinoid. CBD exerts an analgesic effect in several pain models, does not have side effects and has low toxicity. The data about CBD mechanisms of action in pain and its therapeutic potential in this area are limited. Here, we tested CBD effects in animal models specific for migraine. We assayed CBD distribution in plasma and in cranial areas related to migraine pain in male Sprague Dawley rats treated chronically (5 days). Successively, we tested CBD activity on the behavioral and biochemical effects induced in the acute and the chronic migraine animal models by nitroglycerin (NTG) administration. In the acute migraine model, rats received CBD (15 mg or 30 mg/kg, i.p) 3 h after NTG (10 mg/kg i.p.) or vehicle injection. In the chronic migraine model, rats were treated with CBD and NTG every other day over nine days with the following doses: CBD 30 mg/kg i.p., NTG 10 mg/kg i.p. We evaluated behavioral parameters with the open field and the orofacial formalin tests. We explored the fatty acid amide hydrolase gene expression, cytokines mRNA and protein levels in selected brain areas and CGRP serum level. CBD levels in the meninges, trigeminal ganglia, cervical spinal cord, medulla pons, and plasma were higher 1 h after the last treatment than after 24 h, suggesting that CBD penetrates but does not accumulate in these tissues. In the acute model, CBD significantly reduced NTG-induced trigeminal hyperalgesia and CGRP and cytokine mRNA levels in peripheral and central sites. In the chronic model, CBD caused a significant decrease in NTG-induced IL-6 protein levels in the medulla–pons, and trigeminal ganglion. It also reduced CGRP serum levels. By contrast, CBD did not modulate TNF-alpha protein levels and fatty acid amide hydrolase (FAAH) gene expression in any of investigated areas. In both experimental conditions, there was no modulation of anxiety, motor/exploratory behavior, or grooming. These findings show that CBD reaches brain areas involved in migraine pain after systemic administration. They also show for the first time that CBD modulates migraine-related nociceptive transmission, likely via a complex signaling mechanism involving different pathways.

Oral lipid-based formulations alter delivery of cannabidiol to different anatomical regions in the brain

Delivery to the brain is a challenging task due to its protection by the blood–brain barrier (BBB). Lipids and fatty acids are reported to affect the permeability of the BBB, although this has not been reported following oral administration. Cannabidiol (CBD) has high therapeutic potential in the brain, therefore, this work investigated CBD delivery to anatomical brain regions following oral administration in lipid-based and lipid-free vehicles. All formulations resulted in a short brain Tmax (1 h) and brain-plasma ratios ≥ 3.5, with retention up to 18 h post administration. The highest CBD delivery was observed in the olfactory bulb and striatum, and the medulla pons and cerebellum the lowest. The lipid-free vehicle led to the highest levels of CBD in the whole brain. However, when each anatomical region was assessed individually, the long chain triglyceride-rich rapeseed oil formulation commonly showed optimal performance. The medium chain triglyceride-rich coconut oil formulation did not result in the highest CBD concentration in any brain region. Overall, differences in CBD delivery to the whole brain and various brain regions were observed following administration in different formulations, indicating that the oral formulation selection may be important for optimal delivery to specific regions of the brain.

The Peroxidative Changes in Rat Brain Tissue Homogenates by Vitamin C and Deferoxamine against Vanadium-Stimulated Lipid Peroxidation

Objectives Vanadium (V) metal induces lipid peroxidation (LPO) and this has been proposed as a cause for its neurotoxicity. Aim This study aimed to evaluate the effects of vitamin C (VC) and deferoxamine (DF) against V-induced LPO in brain tissue homogenates in vitro. Methods Male Sprague-Dawley rats were used. Brains were removed and dissected into hypothalamus, hippocampus, brain stem, and medulla pons. They were homogenized in150mM potassium chloride (KCl), and incubated for 1 hour with V, VC, and DF in a micromolar concentration of 20 and 100. Aliquots were used for the estimation of LPO in spectrophotometer. Data analysis were done by one-way analysis of variance. Results V exposure (20 and 100μM) demonstrated statistically significant (p < 0.001) enhancement of LPO (average increase with 20μMV was by +105% and with 100μMV was by +130%), respectively, in brain tissue homogenates compared with water controls. Hypothalamus exhibited maximum enhancement (average increase with 20μMV was by +145% and with 100μMV was by +175%, respectively), in LPO than other regions. Coexposure of brain tissue homogenates to V + VC (20 and 100μM) further accelerated the LPO (+24% and +16%, respectively) compared with V alone. Brain stem exhibited highest increases (+54% with 20μMV and +21% with 100μMV; p < 0.001), respectively. V-induced oxidative consequences were remarkably inhibited (average -55%; p < 0.001) by DF + V (20μM + 100μM) exposure. Hypothalamus and medulla pons exhibited inhibition, by −66% and −60% (p < 0.001) respectively. Conclusion V exposure in vitro resulted in oxidative damage with significant regional variations in brain tissue homogenates. VC is pro-oxidative in vitro reactions and DF chelates V-ion moiety.

Antagonism of CGRP Receptor: Central and Peripheral Mechanisms and Mediators in an Animal Model of Chronic Migraine.

Calcitonin-gene-related peptide (CGRP) plays a key role in migraine pathophysiology and more specifically in the mechanisms underlying peripheral and central sensitization. Here, we explored the interaction of CGRP with other pain mediators relevant for neuronal sensitization in an animal model of chronic migraine. Male Sprague-Dawley rats were exposed to nitroglycerin (NTG, 5 mg/kg, i.p.) or vehicle co-administered with the CGRP receptor antagonist olcegepant (2 mg/kg i.p.), or its vehicle, every other day over a 9-day period. Twenty-four hours after the last injection of NTG (or vehicle), behavioral test and ex vivo analysis were performed. Olcegepant attenuated NTG-induced trigeminal hyperalgesia in the second phase of the orofacial formalin test. Interestingly, it also reduced gene expression and protein levels of CGRP, pro-inflammatory cytokines, inflammatory-associated miRNAs (miR-155-5p, miR-382-5p, and miR-34a-5p), and transient receptor potential ankyrin channels in the medulla–pons area, cervical spinal cord, and trigeminal ganglia. Similarly, olcegepant reduced the NTG-induced increase in CGRP and inflammatory cytokines in serum. The findings show that the activation of the CGRP pathway in a migraine animal model was associated to the persistent activation of inflammatory pathways, which was paralleled by a condition of hyperalgesia. These molecular events are relevant for informing us about the mechanisms underlying chronic migraine.

IgG kappa multiple myeloma with isolated central nervous system relapse.

A 76-year-old male presented with acute renal failure and cast nephropathy was diagnosed with IgG kappa multiple myeloma (MM). His paraprotein was 40 g/L, kappa-free light chain level was 17,058 mg/L, kappa: lambda light chain ratio was 1445. An automated full blood count showed hemoglobin 90 g/L, white blood cells 2.96 × 109/L, neutrophil 1.7 × 109/L, and platelet 179 × 109/L. Bone marrow trephine sample was hypercellular with nearly 100% plasma cells, which were positive for CD138, CD56, and cyclin D1, and showed kappa light chain restriction. Fluorescence in situ hybridization analysis with dual color/dual probes for immunoglobulin heavy chain (IGH) and MYC genes (Cytocell) and whole genome screening using 8 × 60K oligonucleotide arrays (Agilent) performed on the CD138 enriched cells (CD138 microbeads Miltenyi Biotech) from the liquid bone marrow sample showed no evidence of IGH rearrangement, MYC rearrangement, 1q gain, 1p loss, 17p loss, or any clinically significant imbalance. He was treated with eight cycles of bortezomib, cyclophosphamide, and dexamethasone (VCD) to very good partial response. He relapsed 30 months after diagnosis with paraprotein of 36 g/L, kappa light chains of 10,000 mg/L, and creatinine of 498 μmol/L. He was treated with eight cycles of bortezomib, thalidomide, and dexamethasone (VTD) to paraprotein undetectable and kappa light chain 29 mg/L. Seven months post completion of VTD (4 years after myeloma diagnosis), he presented with abnormal gait, falls, and a left-sided facial droop. His paraprotein was 2 g/L and serum-free kappa light chain was 81 mg/L. Magnetic resonance imaging (MRI) head and whole spine showed multifocal diseases in spinal canal and intracranially, involving the cranial nerves most prominent the fifth, seventh, eighth, and hypoglossal nerve on the left, anterior surface of the inferior pons medulla (Figure 1A). There were multiple lesions in the cervical spine as well as in the thoracic spine (Figure 1B). Computerized tomography (CT) chest abdomen pelvis did not show the evidence of other new diseases. Plasma cells were detected in cerebral spinal fluid (CSF) (Figure 1C, May–Grünwald–Giemsa stain x100 objective). He was treated with pomalidomide and dexamethasone. Weekly cytarabine intrathecal (IT) treatment was given until the clearance of plasma cells from CSF samples for three times. Four months later, he achieved the complete remission on MRI head and whole spine with undetectable paraprotein and normal light chain ratio. Serial MRI scans confirmed ongoing remission. A year later, he relapsed again with worsening mobility and reappearance of myeloma cells in CSF. By flow cytometry, these cells were positive for CD138, CD38, CD56, CD117, and negative for CD19. MRI head showed leptomeningeal disease with a new 2.2 cm frontal lobe lesion. His paraprotein remained undetectable and kappa light chain remained at below 100 mg/L. He continued systemic pomalidomide and dexamethasone chemotherapy and received palliative whole brain radiotherapy 20 Gy in 5 fractions for symptom control. His disease continued progressing and he passed away 3 months later (5.5 years after myeloma diagnosis). Here, we reported a myeloma patient with isolated CNS relapse, who achieved 1 year of remission with combination of intrathecal chemotherapy and systemic pomalidomide and dexamethasone treatment, but sadly passed away 4 months after second CNS relapse. CNS MM is a rare form of extramedullary disease, but carries a very poor prognosis. The optimal approach to treatment of CNS MM is not currently known. The current approach includes systemic therapy with agents known to cross the blood brain barrier, intrathecal therapy, and CNS irradiation. Innovative approach to treatment is urgently needed. The authors received no specific funding for this work. Ke Xu and Lucy Kamuriwo wrote the manuscript. Ke Xu, Lucy Kamuriwo, Claire Anderson and Parag Jasani critically revised the final version of the manuscript. The authors declare they have no conflicts of interest. No written or verbal consent obtained from patient. Patient has passed away.

Abstract P717: Central Midbrain Strokes Are More Liable for Respiratory Failure Then Other Brain Stem Strokes

Background: Respiratory centers are known to be present in the central medulla oblongata and pons. There are multiple complex respiratory networks involving these centers. The midbrain periaqueductal grey is believed to act as a regulator of the respiratory function. The effect of brain-stem strokes on respiration remains understudied. There is a lack of clear understanding of the anatomical influence of such strokes on respiration. We attempted to identify brain-stem locations with the highest liability for respiratory failure in case of stroke. Methods: We included all ischemic and hemorrhagic brain-stem strokes from our stroke-registry between 2016 and 2018 then performed univariate/multivariate regression-analyses on variables that might predict respiratory failure and the need for intubation. The brain stem was divided into nine locations (right lateral, central, left lateral in each of the midbrain, pons, and medulla oblongata). Results: Out of 128 brain-stem strokes of different sizes and etiologies, central midbrain strokes were the only significant and independent affected location associated with respiratory failure and endotracheal intubation (coefficient= 0.1256, 95%-CI= 0.0175, 0.2338, p= 0.023). R-squared was equal to 15% when only central midbrain strokes stayed in the model. Conclusions: While one might assume that central medullary and pontine strokes have the most impact on respiration; our results show that central midbrain is the most impactful, accounting for about 15% of respiratory instability associated with brain-stem strokes. This can be explained by the adaptive nature of respiratory circuits within the medulla and pons. Central periaqueductal grey within the midbrain controls the rate and depth of respiration and might not have the same flexibility present elsewhere.

Concurrent brain structural and functional alterations in patients with migraine without aura: an fMRI study

ObjectivesTo explore the possible concurrent brain functional and structural alterations in patients with migraine without aura (MwoA) patients compared to healthy subjects (HS).MethodsSeventy-two MwoA patients and forty-six HS were recruited. 3D-T1 and resting state fMRI data were collected during the interictal period for MwoA and HS. Voxel-based morphometry (VBM) for structure analysis and regional homogeneity (Reho) for fMRI analysis were applied. The VBM and Reho maps were overlapped to determine a possible brain region with concurrent functional and structural alteration in MwoA patients. Further analysis of resting state functional connectivity (FC) alteration was applied with this brain region as the seed.ResultsCompared with HS, MwoA patients showed decreased volume in the bilateral superior and inferior colliculus, periaqueductal gray matter (PAG), locus ceruleus, median raphe nuclei (MRN) and dorsal pons medulla junction. MwoA patients showed decreased Reho values in the middle occipital gyrus and inferior occipital gyrus, and increased Reho values in the MRN. Only a region in the MRN showed both structural and functional alteration in MwoA patients. Pearson correlation analysis showed that there was no association between volume or Reho values of the MRN and headache frequency, headache intensity, disease duration, self-rating anxiety scale or self-rating depression scale in MwoA patients. Resting state functional connectivity (FC) with the MRN as the seed showed that MwoA patients had increased FC between the MRN and PAG.ConclusionsMRN are involved in the pathophysiology of migraine during the interictal period. This study may help to better understand the migraine symptoms.Trial registrationNCT01152632. Registered 27 June 2010.

Histochemical analysis of 3β-hydroxysteroid dehydrogenase activity in neurons of the brain stem in rats

The histochemistry method was used to study the activity of 3β-hydroxysteroid dehydrogenase (GSDG) in the neurons of the medulla oblongata and the pons medulla. It was revealed that GSDG-positive neurons are detected by this method in neurons of the nucleus (giant cell, para giant cell, intermediate reticular, medial vestibular and others), as well as in the internuclear zones. Spectrophotometric analysis showed that the intensity of the response to GDD in cells of the brain stem is high and in neurons of the giant cell nucleus exceeds that in Purkinje cells of the cerebellar cortex.

Immunohistochemical evaluation of natural cases of encephalitic listeriosis in sheep

ABSTRACTListeriosis is an important public health problem in the world. It can cause abortion, encephalitis, septicemia, conjunctivitis and mastitis in ruminants. The development of central nervous system lesions is not fully understood in encephalitic listeriosis. We performed a retrospective analysis of 15 sheep with encephalitic listeriosis. Hyperemia and opacification of the meninges were common necropsy findings. Lesions generally were localized in the caudal part of the brain including the pons, medulla oblongata, thalamus and cerebellum. Microabscesses usually were found in the caudal brain and cerebellum, while perivascular infiltrates were found most often in other parts of the brain. Evidence of Listeria monocytogenes was detected immunohistochemically in the medulla oblongata, pons, thalamus and cerebellum. Prominent reactions for glial fibrillary acidic protein (GFAP), S100 protein, N-methyl-D-aspartate receptor-1 (NMDAR1) and inducible co-stimulatory protein (ICOS) were detected in the caudal brain, which indicates that these proteins may play roles in the pathogenesis of encephalitic listeriosis.

Anticonvulsant effect of Bacopa monnieri extracts on Catecholamine metabolism during PTZ-induced Epilepsy in different brain regions of Albino Rat

In the modern era, Epilepsy is one of the most prevalent serious neurological disorders, affecting 0.5 to 1.0% of the world’s population. Epileptic seizures are paroxysmal clinical events arising from neuronal hyper-excitability and hypersynchrony of the cerebral cortex, either locally (partial seizures) or diffusely in both hemispheres (generalized seizures). The agitated neuronal activity that occurs during a seizure is caused by a sudden imbalance between the inhibitory and excitatory signals in the brain with glutamate, ?-aminobutyric acid (GABA), noradrenaline, serotonin, and dopamine. Since long term usage of antiepileptic drugs cause high incidence of pharmacoresistence and untoward side effects, attention has been paid in recent years to screen bioactive compounds from natural medicinal plants for treatment of several neurological disorders including Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study was designed to assess the neurotoxicity of PTZ on the metabolism of Biogenic amines (Nor-epinephrine, Epinephrine, Dopamine, Serotonin) in different brain regions (Cerebral cortex, Cerebellum, Pons medulla and Hippocampus) of rat and explore the possible antiepileptic effect of different extracts (Ethanol, n-Hexane, Chloroform, Ethyl acetate, n-Butanol and Aqueous extracts) of BM in comparison with Diazepam (DZ) (Reference control). PTZ-Induced epilepsy caused significant decrease in all the catecholamine levels in all brain regions. On par with Diazepam pretreatment, different extracts of BM except aqueous extract (AE) significantly increased the monoamine contents in all the regions of brain. Mono amine oxidase (MAO) activity levels showed elevation in different brain regions of rat during PTZ-induced epilepsy which was reversed in epileptic animals pretreated with different extracts except AE and DZ. These findings suggest that BM causes perceptible changes in the biogenic amine metabolism as one of the major facets of its anticonvulsant activity. Hence, BM extract can be effectively used in the treatment of Epilepsy and other related neurological disorders.

Alterations in the Glutamate metabolism and Aminotransferases (AAT, ALAT) during PTZ – induced Epilepsy: Protective role of Bacopa monnieri

Epilepsy, a common chronic neurological disorder characterized by repeated, spontaneous seizures, also known as seizure disorder. Seizure related neuronal injury has been assumed to be mediated by glutamate, the excitatory amino acid, in the central nervous system that causes a sudden imbalance between the inhibitory and excitatory signals in the brain with glutamate, γ-aminobutyric acid (GABA), noradrenaline, serotonin, and dopamine. Since long term usage of antiepileptic drugs cause high incidence of pharmacoresistence and untoward side effects, attention has been paid in recent years to screen bioactive compounds from natural medicinal plants for treatment of several neurological disorders including Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study is designed to assess the neurotoxicity of Pentylene tetrazole (PTZ), an epileptic compounds, on the Glutamate metabolism and Amino transferases in different brain regions (Cerebral cortex, Cerebellum, Pons medulla and Hippocampus) of rat and to explore the possible antiepileptic effect of different extracts (Ethanol, n-Hexane, Chloroform, Ethyl acetate, n-Butanol and Aqueous extracts) of BM in comparison with Diazepam (DZ) (Reference control). The activities of glutamate dehydrogenase (GDH), glutamine synthetase (GS) and glutamine content were decreased in different regions of brain during PTZ induced epilepsy which were increased in epileptic rats pretreated with different extracts of Bacopa monnieri except EAE and AE. Glutaminase activity was increased in PTZ induced epilepsy and decreased on pretreatment with all the extracts of BM except AE. In addition aspartate (AAT) and alanine aminotransferase (ALAT) activity levels were increased during PTZ induced epilepsy when compared with normal control and levels were reversed on pretreatment with different extracts of BM. Recoveries of these parameters during antiepileptic treatment suggest that the bioactive factors present in the extracts offer neuroprotection by interrupting the pathological cascade of glutamatergic hyperexcitation that occurs during epileptogenesis.

English

A study was carried out on the effect of varied levels of dietary aflatoxin on acetylcholinesterase, glucose and total protein concentration in the brain regions of West African Dwarf goats. 20 West African Dwarf goats of about 5-6 months old were used for the trial and they were randomly allotted to four dietary treatments containing 0 (control), 50, 100 and 150 µg aflatoxin/kg diet. The animals were housed individually for the feeding trial in a completely randomised designed and the experiment lasted 12 weeks. At the end of the feeding trial, the animals were sacrificed and brain dissected into different regions. The different regions of the brain studied were medulla oblongata, amygdala, hippocampus, cerebral cortex, mid-brain, cerebellum, pons varoli and hypothalamus. Samples were collected from these regions and homogenised to determine acetylcholinesterase, glucose and total protein concentrations. Result showed that the acetylcholinesterase activity in the brain regions was not significantly influenced by the dietary aflatoxin among the treatments. Glucose concentration was significantly (p<0.05) higher in the hypothalamus of animals fed 50 µg aflatoxin/kg and control diet than those fed 100 and 150 µg aflatoxin/kg. Total protein concentration in the medullar oblongata and the hypothalamic regions of the brain in animals fed 150 ppb was significantly (p<0.05) higher than those on the control diet. The pH of the medulla oblongata, amygdala, hippocampus, cerebral cortex were significantly (p<0.05) higher in goats fed 150 mg/kg than those fed the control diet. However, pH was not significant in the mid brain, cerebellum, pons varoli and hypothalamus among the treatments. This study suggests that dietary aflatoxin up to 100 ppb reduced glucose concentration in the hypothalamus and total protein in the medulla oblongata region of the brain with tendency to impair brain function. Key words: Aflatoxin, WAD goat brain, acetylcholinesterase, total protein.

Concentration of Serotonin And 5 Hydroxy Indole Acetic Acid in Discrete Brain Regions of Overiectomized And Estradiol Treated Female Rats

Back Ground: Estrogen is the sex hormone that causes the development and maintenance female secondary sexual characters. Post menopausal women increasing in vulnerable to depression due to the reduced estrogen production. The activity of estrogen on serotonin has anti depressant characteristics. A higher level serotonin activity is associated with Positive mood while decreased activity is associated with depressive mood. Estrogen boosts the activity of serotonin. Objectives: To determine the brain serotonin and its major metabolite 5HIAA in ovariectomized rats at different day intervals and after estradiol treatment. Methodology: Female albino rats of wister strain where ovariectomized and treated with ethanyl estradiol, Brain serotonin and 5HIAA was estimated by Fluoremetric method. Data was analysed by student’s t test. Result: Reduction in serotonin and 5HIAA level in Hypothalamus, striatum and pons medulla after ovariectomy and increased in estradiol treated rats. Conclusion: Estrogen may be used as effective anti depressant after further studies.

Comparative Study of Catecholaminergic and Nitroxidergic Neurons in the Vasomotor Nuclei of the Caudal Part of the Brainstem in Rats

Immunohistochemical studies in 12 Wistar rats detected tyrosine hydroxylase (TH) and the neuronal form of nitric oxide synthase (nNOS) to address the distribution of catecholaminergic and nitroxidergic neurons, respectively, in the vasomotor nuclei of the medulla oblongata and pons. The highest frequency of TH expression was seen in neurons located in these nuclei and some reticular nuclei (the gigantocellular, paragigantocellular, and caudal nuclei of the pons), though the proportions of immunoreactive neurons in these structures were no greater than 8–14%. In other nuclei (the reticular parvocellular and oral nucleus of the pons, the spinal nucleus of the trigeminal nerve), this proportion ranged from 1 to 3%. Neurons of this type were consistently not detected in a large group of nuclei with confirmed vasomotor functions. Structures with many catecholaminergic neurons generally contained fewer nNOS-positive cells than nuclei with limited numbers of TH-positive neurons.

Effects of Repeated Low-Dose Exposure of the Nerve Agent VX on Monoamine Levels in Different Brain Structures in Mice

In a previous report, alterations of the serotonin metabolism were previously reported in mice intoxicated with repeated low doses of soman. In order to better understand the effects induced by repeated low-dose exposure to organophosphorus compounds on physiological and behavioural functions, the levels of endogenous monoamines (serotonin and dopamine) in different brain areas in mice intoxicated with sublethal dose of (O-ethyl-S-[2(di-isopropylamino) ethyl] methyl phosphonothioate) (VX) were analysed by HPLC method with electrochemical detection. Animals were injected once a day for three consecutive days with 0.10 LD50 of VX (5 μg/kg, i.p). Neither severe signs of cholinergic toxicity nor pathological changes in brain tissue of exposed animals were observed. Cholinesterase (ChE) activity was only inhibited in plasma (a maximum of 30% inhibition 24 h after the last injection of VX), but remained unchanged in the brain. Serotonin and dopamine (DA) metabolism appeared significantly modified. During the entire period of investigation, at least one of the three parameters investigated (i.e. DA and DOPAC levels and DOPAC/DA ratio) was modified. During the toxic challenge, an increase of the serotonin metabolism was noted in hippocampus (HPC), hypothalamus/thalamus, pons medulla and cerebellum (CER). This increase was maintained 4 weeks after exposure in HPC, pons medulla and CER whereas a decrease in cortex 3 weeks after the toxic challenge was observed. The lack of correlation between brain ChE activity and neurochemical outcomes points out to independent mechanisms. The involvement in possibly long-lasting behavioural disorders is discussed.

Osmotic demyelination syndrome as the initial manifestation of a hyperosmolar hyperglycemic state.

Osmotic demyelination syndrome (ODS) is a life-threatening demyelinating syndrome. The association of ODS with hyperosmolar hyperglycemic state (HHS) has been seldom reported. The aim of this study was to present and discuss previous cases and the pathophysiological mechanisms involved in ODS secondary to HHS. A 47-year-old man arrived to the emergency room due to generalized tonic-clonic seizures and altered mental status. The patient was lethargic and had a Glasgow coma scale of 11/15, muscle strength was 4/5 in both lower extremities, and deep tendon reflexes were diminished. Glucose was 838 mg/dL; serum sodium and venous blood gas analyses were normal. Urinary and plasma ketones were negative. Brain magnetic resonance revealed increased signal intensity on T2-weighted FLAIR images with restricted diffusion on the medulla and central pons. Supportive therapy was started and during the next 3 weeks the patient progressively regained consciousness and muscle strength and was able to feed himself. At 6-month follow-up, the patient was asymptomatic and MRI showed no residual damage. In conclusion, the association of ODS with HHS is extremely rare. The exact mechanism by which HHS produces ODS still needs to be elucidated, but we favor a rapid hypertonic insult as the most plausible mechanism.

Role of rostral medulla in serotonin-induced changes of respiratory rhythm in newborn rat brainstem–spinal cord preparations

Abnormalities of the serotonin (5-hydroxytryptamine, 5-HT) system may induce respiratory disorders. We examined which regions in the rostral medulla are important for the effect of 5-HT on the frequency of respiratory-like nerve (fR-like) activity by transecting the preparations at different levels near the facial nucleus (nVII) in newborn rat brainstem–spinal cord preparations. The fR-like activity at the fourth cervical ventral root (C4) of the Pons–medulla–spinal cord preparations in 2–3-day-old rats (n=25) was monitored at 26°C, and the change in fR-like activity in response to application of 10μM 5-HT before and after transection was compared among three groups, in which nVII was retained (group A, n=10), partially retained (group B, n=7), or eliminated (group C, n=8) by the transection. Before transection, the resting fR-like activity (set to 100%) and stimulant effect of 5-HT (+101–143%) were similar among the groups. After transection, resting fR-like activity increased in all groups, but the facilitatory effects of 5-HT on the fR-like activity were abolished in groups A and C (fR-like activity of −4% and +7%, respectively). In group B, 5-HT became inhibitory (fR-like activity of −28%). In conclusion, a distinct part of the rostral medulla in the absence of pontine influences may mediate the inhibitory effects of 5-HT on the respiratory rhythm.

Distribution of Heme Oxygenase-2 in the Brainstem Nuclei of Rats

Immunocytochemical method was used to determine the distribution of neurons expressing heme oxygenase-2 (HO-2-positive neurons) in the nuclei of various parts of the brainstem of 16 male Wistar rats. The sizes of neurons and the optical density of the product of histochemical reaction in their cytoplasm were determined in the nuclei studied. HO-2-positive neurons, differing in shape, size and numbers, were identified in the nuclei of the medulla oblongata, pons and midbrain. HO-2-positive cells were found 3-5 times more frequently in the sensory nuclei as compared to the motor ones. At the same time, relatively large number of nuclei was detected, which contained either no or a few HO-2-positive neurons.