Antioxidant extract counteracts the effects of aging on cortical spreading depression and oxidative stress in the brain cortex

Abstract Purpose: To investigate the effects of Murici extract on the brain excitability-dependent phenomenon known as cortical spreading depression (CSD) and on brain oxidative stress. Methods: Adult and aged Wistar rats were supplemented with murici extract (150 mg/kg/day or 300 mg/kg/day) by gavage for fifteen days. Afterwards, the animals were submitted to a CSD electrophysiological recording and to brain oxidative stress evaluation. Results: Our results showed that aging decreased CSD propagation velocity, catalase activity and glutathione/oxidized glutathione ratio (GSH/GSSG) in the brain cortex of the rats, and increased malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activity. The highest dose (300 mg/kg/day) of murici extract accelerated CSD, whereas the lowest (150mg/kg/day) decelerated, in both adult and aged animals. In contrast, aged animals supplemented with murici extract in both doses presented low MDA levels and high GSG/GSSG ratio in comparison to the control-aged animals. Conclusion: Murici extract supplementation seems to revert detrimental effects in aged brains and could be considered as a strategy in the treatment of pathologies related to aging and cortical spreading depression.

Effects of crocin on brain oxidative damage and aversive memory in a 6-OHDA model of Parkinson's disease / Efeitos da crocina no dano oxidativo cerebral e na memória aversiva em um modelo 6-OHDA de doença de Parkinson

ABSTRACT The purpose of the present study was to investigate the effect of crocin on brain oxidative damage and memory deficits in a 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. Male Wistar rats were subjected to unilateral injection of 6-OHDA (16 µg) into the medial forebrain bundle and treated with crocin (30 and 60 mg/kg) for six weeks. The rats were tested for memory performance at six weeks after 6-OHDA infusion, and then were killed for the estimation of biochemical parameters. The increase in thiobarbituric acid reactive substances (TBARS) and nitrite levels in the hippocampus were observed in the 6-OHDA lesioned rats, which was accompanied by memory deficits in a passive avoidance test at the end of week 6. Moreover, treatment with crocin decreased TBARS and nitrite levels in the hippocampus, and improved aversive memory. The present study conclusively demonstrated that crocin acts as an antioxidant and anti-inflammatory agent in the hippocampus of parkinsonian rats and could improve aversive memory through its properties.

RESUMO O objetivo do presente estudo foi investigar o efeito da crocina no dano oxidativo cerebral e nos déficits de memória em um modelo 6-OHDA de doença de Parkinson. Ratos Wistar machos foram submetidos à injeção unilateral de 6-OHDA (16 μg) em MFB e tratados com crocina (30 e 60 mg/kg), durante 6 semanas. Os ratos foram testados quanto ao desempenho da memória 6 semanas após a infusão de 6-OHDA, e, em seguida, foram sacrificados para a estimativa dos parâmetros bioquímicos. O aumento nos níveis de TBARS e de nitrito no hipocampo foram observados em ratos 6-OHDA lesionados, acompanhado por déficits de memória em um teste de esquiva passiva no final da semana 6. Além disso, o tratamento com crocina diminuiu os níveis de nitrito e de TBARS no hipocampo e melhorou a memória aversiva. O presente estudo demonstrou conclusivamente que a crocina age como um antioxidante e um agente anti-inflamatório no hipocampo de ratos parkinsonianos e pode melhorar a memória aversiva através de suas propriedades.

Beneficial effects of glucan against cisplatin side effects on the nervous system in rats 1

ABSTRACT PURPOSE: To investigate the protective effect of Bg on cisplatin (CP)-induced neurotoxicity in rats. METHODS: Twenty eight rats were randomly distributed into four groups. The first group was kept as a control. In the second group, CP was given at the single dose of 7 mg/kg intraperitoneally. In the third group, βg was orally administered at the dose of 50 mg/kg/day for 14 days. In the fourth group, CP and βg were given together at the same doses. RESULTS: CP treatment caused significant oxidative damage via induction of lipid peroxidation and reductions antioxidant defense system potency in the brain tissue. In addition, histopathological damage increased with CP treatment. On the other hand, βg treatment largely prevented oxidative and histopathological negative effects of CP. CONCLUSIONS: Cisplatin has severe neurotoxic effects in rats and βg supplementation has significant beneficial effects against CP toxicity depending on its antioxidant properties. Thus, it appears that βg might be useful against CP toxicity in patients with cancer in terms of nervous system.

Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

Gongronema latifolium modulates Rauwolfia vomitoria-induced behaviour and histomorphology of the cerebral cortex / Gongronema latifolium modula los cambios de comportamiento e histomorfología de la corteza cerebral inducidos por Rauwolfia vomitoria

Rauwolfia vomitoria (RV) has potent sedative effect, which may result in severe unpleasant consequences if not controlled. This necessitated this study on the effect of Gongronema latifolium (GL) on RV-induced behaviour, biochemical activities, and histomorphology of the cerebral cortex. Eighteen male Wistar rats of average weight 266 g were grouped into three (1­3). Group 1 was the control administered 0.5 mL of Tween®20, while groups 2 and 3 were administered 150 mg/kg of RV, and a combination of 150 mg/kg of RV and 200 mg/kg of GL (RV+GL), respectively for seven days. Twelve hours after treatments, open field neurobehavioral test was carried-out and the animals euthanized. Their sera were analyzed, and their cerebral cortices routinely processed by H&E method. There was lower (p<0.05) ambulatory, rearing and freezing activities in the RV group, while there was no difference in aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities, as well as serum cholesterol and triglycerides levels in all the groups. Cerebral cortical neurohistology of RV and RV+GL groups showed most neurons appearing hypertrophied with pyknotic nuclei in some, and less cellular population compared with the control group. RV produces sedative behaviour, and cerebral cortical neurohistological changes, which GL combination may help modulate.

Rauwolfia vomitoria (RV) tiene un efecto sedante potente, el que puede provocar graves consecuencias si no es controlado. Se estudió el efecto de Gongronema latifolium (GL) sobre el comportamiento inducido por RV, como también en las actividades bioquímicas, e histomorfología de la corteza cerebral. Dieciocho ratas macho Wistar con un peso promedio de 266 g, fueron separadas en tres Grupos (1­3). El Grupo 1 (control) recibió 0,5 mL de Tween® 20, mientras que a los Grupos 2 y 3 se les administró, durante siete días, 150 mg/kg de RV y una combinación de 150 mg/kg de RV y 200 mg/kg de GL (RV + GL), respectivamente. Doce horas después de los tratamientos y pruebas neuroconductuales de campo abierto, los animales fueron sacrificados. Se analizaron los sueros y cortezas cerebrales, los cuales fueron procesados y teñidos on HE. Se observó menor actividad ambulatoria y de congelación (p<0,05) en el grupo RV, mientras que no hubo diferencia en la actividad aspartato aminotransferasa sérica y de fosfatasa alcalina, así como tampoco en los niveles de colesterol y triglicéridos séricos en todos los grupos. La neurohistología cortical cerebral de los grupos RV y RV + GL mostró que la mayoría de las neuronas aparecen hipertrofiadas con núcleos picnóticos, y una menor cantidad celular en comparación con el grupo control. La RV produce un comportamiento sedante, y cambios neurohistológicos a nivel de la corteza cerebral lo que podría ser modulado al combinarse con GL.

Ulinastatin attenuates oxidation, inflammation and neural apoptosis in the cerebral cortex of adult rats with ventricular fibrillation after cardiopulmonary resuscitation

OBJECTIVE: The role of Ulinastatin in neuronal injury after cardiopulmonary resuscitation has not been elucidated. We aim to evaluate the effects of Ulinastatin on inflammation, oxidation, and neuronal injury in the cerebral cortex after cardiopulmonary resuscitation. METHODS: Ventricular fibrillation was induced in 76 adult male Wistar rats for 6 min, after which cardiopulmonary resuscitation was initiated. After spontaneous circulation returned, the rats were split into two groups: the Ulinastatin 100,000 unit/kg group or the PBS-treated control group. Blood and cerebral cortex samples were obtained and compared at 2, 4, and 8 h after return of spontaneous circulation. The protein levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were assayed using an enzyme-linked immunosorbent assay, and mRNA levels were quantified via real-time polymerase chain reaction. Myeloperoxidase and Malondialdehyde were measured by spectrophotometry. The translocation of nuclear factor-κB p65 was assayed by Western blot. The viable and apoptotic neurons were detected by Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). RESULTS: Ulinastatin treatment decreased plasma levels of TNF-α and IL-6, expression of mRNA, and Myeloperoxidase and Malondialdehyde in the cerebral cortex. In addition, Ulinastatin attenuated the translocation of nuclear factor-κB p65 at 2, 4, and 8 hours after the return of spontaneous circulation. Ulinastatin increased the number of living neurons and decreased TUNEL-positive neuron numbers in the cortex at 72 h after the return of spontaneous circulation. CONCLUSIONS: Ulinastatin preserved neuronal survival and inhibited neuron apoptosis after the return of spontaneous circulation in Wistar rats via attenuation of the oxidative stress response and translocation of nuclear factor-κB p65 in the cortex. In addition, Ulinastatin decreased the production of TNF-α, ...

Superoxide dismutase functional regulation in neonatal hypoxia: Effect of glucose, oxygen and epinephrine.

Hypoxia is one of the major causes of damage to the fetal and neonatal brain and cardiac functions. In earlier studies, we have reported the brain damage caused by hypoxia and resuscitation with oxygen and epinephrine and have found that glucose treatment to hypoxic rats and hypoxic rats treated with oxygen shows a reversal of brain damage. The neonatal rats are shown to be deficient in free radical scavenging system, which offers a high risk of oxidative stress. In the present study, we induced hypoxia in neonatal Wistar rats and resuscitated with glucose, oxygen and epinephrine. Heart tissue and cerebral cortex were used to study the kinetics of superoxide dismutase activity in experimental groups of rats to assess the free radical status. Results showed that glucose supplementation in hypoxia (Hx + G) and hypoxic + oxygen (Hx + O) had an efficient free radical scavenging capability, compared to all other experimental groups. The observation was ascertained by studying the activity of catalase, another antioxidant enzyme in the body. Our results suggested that in neonatal rats during hypoxic condition, damage to heart and brain was more prominent in all groups, except when supplemented with glucose. These findings may have clinical significance in the proper management of heart and brain function.

Anti-nociceptive effect of duloxetine in mouse model of diabetic neuropathic pain.

The involvement of adenosinergic pathway in the anti-nociceptive effect of duloxetine, a balanced 5-HT/NE reuptake inhibitor, was evaluated in streptozotocin induced diabetic male albino mice of Laca strain. After four weeks of single injection of streptozotocin (200 mg/kg, ip), mice were tested in the tail immersion and hot-plate assays. Cerebral adenosine levels were measured by high-performance liquid chromatography (HPLC/PDA detector). Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose, decreased body weights and reduced cerebral adenosine levels. Administration of duloxetine (5, 10 and 20 mg/kg, ip) to diabetic mice produced dose-dependent anti-nociceptive effect in both tail-immersion and hot-plate assays. Adenosine levels were also significantly and dose-dependently increased by different doses of duloxetine. The results demonstrated the involvement of adenosinergic pathway in duloxetine mediated anti-hyperalgesia in diabetic neuropathic pain.

Establishment and evaluation of animal model with methamphetamine poisoning / 法医学杂志

Amphetamine-type stimulants (ATS) is the most widespread narcotics in the 21st century. The methamphetamine's intoxication mechanism, psychological dependence, drug resistance and therapeutic drug development are the hot spots in current research. Establishment of animal model with methamphetamine poisoning is the basic for the relative studies, the normalization and standardization of the animal model settles the foundation for methamphetamine's further research. This article reviews the animal model of methamphetamine poisoning in China and abroad, the brief history of the acute, subacute and chronic animal model of methamphetamine poisoning, as well as the principles and methods of the animal model establishment and its evaluation criteria. The necessity, significance and its scientific expansion of performing experimental research on the methamphetamine poisoning animal model are also discussed.

Small-molecule aggregation inhibitors reduce excess amyloid in a trisomy 16 mouse cortical cell line

We have previously characterized a number of small molecule organic compounds that prevent the aggregation of the β-amyloid peptide and its neurotoxicity in hippocampal neuronal cultures. We have now evaluated the effects of such compounds on amyloid precursor protein (APP) accumulation in the CTb immortalized cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down's syndrome. Compared to a non-trisomic cortical cell line (CNh), CTb cells overexpress APP and exhibit slightly elevated resting intracellular Ca2+ levéis ([Ca2+]¡). Here, we show that the compounds 2,4-dinitrophenol, 3-nitrophenol and 4-anisidine decreased intracellular accumulation of APP in CTb cells. Those compounds were non-toxic to the cells, and slightly increased the basal [Ca2+]¡. Results indícate that the compounds tested can be leads for the development of drugs to decrease intracellular vesicular accumulation of APP in trisomic cells.

A reviewing for abusing of ketamine / 法医学杂志

Ketamine is a noncompetitive NMDA receptor antagonist and comes into being a new problem of drug abuse. It can cause a certain extent of hallucination, which makes ketamine be abused in the casinos. The paper reviews the pharmacological and toxicology characteristic of Ketamine, the possible physiological mechanism and the methods for detecting Ketamine abuse.

Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo

A degree of brain inflammation is required for repair of damaged tissue, but excessive inflammation causes neuronal cell death. Here, we observe that IL-10 is expressed in LPS-injected rat cerebral cortex, contributing to neuronal survival. Cells immunopositive for IL-10 were detected as early as 8 h post-injection and persisted for up to 3 d, in parallel with the expression of IL-1beta, TNF-alpha, and iNOS. Double immunofluorescence staining showed that IL-10 expression was localized mainly in activated microglia. Next, we examined the neuroprotective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action caused a significant loss of neurons both 3 d and 7 d after LPS injection. Further, the induction of mRNA species encoding IL-1beta, TNF-alpha, and iNOS, reactive oxygen species (ROS) production, and NADPH oxidase activation, increased after co-injection of LPS and IL-10NA, compared to the levels seen after injection of LPS alone. Taken together, these results clearly suggest that LPS-induced endogenous expression of IL-10 in microglia contributes to neuronal survival by inhibiting brain inflammation.

Thinner abuse alters peak of frequency of EEG spectra analyses / El abuso de tíner altera el pico de frecuencia del análisis espectral del EEG

STUDY OBJECTIVE: The aim of the investigation was to use electroencephalography (EEG) to study whether long-term thinner abuse may result in the slowing, disorganization and asymmetry of the EEG cortical rhythms. METHOD: Twenty-two patients attending with antecedent of thinner abuse only, and twenty two controls without alcohol, smoking, and drug abuse in the same age range and gender were studied. EEG recording were compared by means of the analyses of peak of frequency (POF), frequency of disorganization, and asymmetry of the background activity in patients and controls at rest eyes-closed condition in electrodes P3, P4, O1, and O2. RESULTS: Significant differences in POF among groups was observed in P3 and P4 location showing lower values in thinner abusers, but not in O1 and O2 locations. Frequencies of disorganization and asymmetry showed significantly higher proportions in thinner abusers. Bivariate correlations among POF at the four electrode location and time of thinner abuse showed significant values. However after partial correlation calculation correcting for age, significant values disappeared. CONCLUSION: Thus thinner abuse relates with slowing of POF in the EEG of patients with thinner abuse associated with disorganization, and asymmetry depending on time of abuse.

OBJETIVO: Utilizar el electroencefalograma (EEG) para estudiar si el abuso o intoxicación crónica por tíner produce lentificación, desorganización y asimetría de la actividad eléctrica cortical. MÉTODO: Se estudiaron 22 pacientes con antecedentes de intoxicación crónica por tíner y 22 sujetos sin antecedentes de abuso de tíner, alcohol, cigarro o drogas en el mismo rango de edad y en igual número de acuerdo al género. Se registro el EEG cuantitativo y se compararon: el promedio del pico de frecuencia (PoF), la frecuencia de desorganización de la actividad de fondo y la presencia de asimetría inter-hemisférica en la condición de reposo físico y mental entre las regiones de los electrodos P3, P4, O1 y O2. RESULTADOS: Se encontraron diferencias significativas en el PoF entre los grupo estudiados en P3 y P4 observándose valores menores en el grupo con antecedente de intoxicación crónica con tíner, sin embargo estas diferencias no fueron observadas en O1 y O2. La frecuencia de desorganización y de asimetría fue mayor entre los pacientes con antecedente de intoxicación crónica con tíner. Las correlaciones bivariadas entre el PoF en las cuatro localizaciones y el tiempo de consumo de tíner mostraron valores significativos, sin embargo, cuando fueron corregidas por la edad desaparecieron. CONCLUSION: La intoxicación crónica por tíner se relaciona a una lentificación del PoF del EEG de estos pacientes asociada con desorganización y asimetría que dependen parcialmente del tiempo de consumo.

Neuroembryotoxic effect of 5- Fluorouracil in rat: injecting in late phase of gestation.

Macro and microscopic findings in developing brain of rat fetuses were observed after intraperitoneal injection with a single dose (30mg/kg) of 5-Fluorouracil (5-FU) in late phase of gestation. 5-FU induced more than 60.0% lethality with significant reduction (p<0.001) in weight and various dimensions of the developing brain. Macroscopic findings of the developing brain revealed microcephaly, regression or absence of the olfactory lobe and obliteration of the various fissures on the dorsal surface. Microscopic examination of the olfactory lobe of treated brain showed the obliteration of the olfactory ventricle, distortion of the cellular arrangement of various layers of the olfactory cortex with clumping of degenerated neurons and glial cells. Cerebral cortex of the treated brain revealed the distortion of normal cytoarchitecture of the various cortical layers. The neurons of the treated brain revealed the degeneration, deeply stained eccentric nucleus with loss of mitotic figures and pyknotic changes. Subcortical zone of the treated cerebrum showed the degenerative changes in the fibrous structure along with paucity of the glial cells. The hippocampus of the treated brain revealed the loss of normal cytoarchitecture and shrinkage of all the layers. Neuroembyopathic effect of 5-FU is severe, when given in late phase of pregnancy, so it is advisable that the drug should be avoid during the late period of pregnancy.

Cerebral electrical activity as a tool in evaluating anesthetic effect during balanced anesthesia with sevoflurane.

OBJECTIVES: The present study was undertaken to provide basic information about bilateral frontal cerebral electrical activity after induction, before and after skin incision, and at a steady state during sevoflurane anesthesia at the end tidal concentration 1, 1.2, 1.4 and 1.6 MAC and determine the association between the electrical cerebral activity with other clinical end points, i.e. motor responses and post-operative recall. MATERIAL AND METHOD: the Dual Channel Brain Activity, ABM2 (DATEX) was used to continuously monitor frontal EMG and electrical cerebral activities (i.e. frequency and amplitude) of both hemispheres in 20 adult female patients undergoing balanced anesthesia in Maharaj Chiang Mai Hospital. The eligible patients were randomly assigned to receive 1.0 MAC, 1.2MAC, 1.4MAC or 1.6MAC of a mixture of sevoflurane and 66.67% nitrous oxide in oxygen during anesthesia. The anesthesia was induced with 5 mg/kg thiopental and supplemented with 1-1.5 microgram per kilogram of fentanyl. The standard dose of pancuronium or atracurium was given during maintenance. RESULTS: After induction with 5 mg/kg thiopental, the mean (95% confidence interval) of frontal EMG significantly decreased from 2.66 (1.63,4.29) to 1.41 (0.2,1.61). When eyelash reflex was absent, the mean (95%CI) frequency and amplitude of the right frontal EEG was 3.89 (3.29, 4.497) Hz, 39.58 (32.11, 47.05) microvolt and left frontal EEG was 3.84 (3.43, 4.25) Hz, 33.55 (28.59, 38.61) microvolt. The findings were consistent with the raw EEG shown on the monitor, i.e. a progressive decrease in the frequency and an increase in the amplitude. During maintenance with the inhaled anesthetics, there was a statistically significant decrease in frequency of right frontal in those who had received the inhaled anesthetic concentration to reach 1.4 and 1.65 MAC (p < 0.05) (repeated measure ANOVA). At the steady state of end tidal concentration of the sevoflurane there was consistency in decreasing frequencies and increasing amplitudes of both hemispheres of the groups with higher MAC values (p < 0.05) (Table 3). However, the authors failed to demonstrate the relationships between EEG changes and other clinical responses. CONCLUSION: The present study has provided basic information about cerebral electrical activity during the balanced anesthesia with sevoflurane. As anesthesia deepened by increased MAC, the frequency decreased and the amplitude increased.

toxic effect of prolonged ultram administration on cerebral cortex of albino rats. Toxicological and histological study

Ultram [Tramadol] is a widely used opioid analgesic effective in treating both acute and chronic pains and has acceptable adverse effects. The aim of the present study was to evaluate the cerebrocortical toxicity resulting from one month and two month Ultram administration in to albino rats using biochemical and histological parameters. The study was carried out on 25 adult male albino rats divided into: control group received 0.5 ml /day saline orally by orogastric tube for two months, a short-term Ultram-treated group that received a dose of 30 mg/kg/day [1/10 LD50] for one month orally and a long-term Ultram-treated group that received the same dose for two months. The study revealed that Ultram administration caused a significant elevation of serotonin level in the cerebral cortical tissues of rats which was directly proportional to the duration of Ultram admistration. Histologically, there were many changes in the organization and ultrastructure of neurons in the different layers of cerebral cortex associated with an increased response of the supporting neuroglial cells. Intense neurological tissue lesions were more evident with the two months Ultram dosing than with one month. The correlation between the biochemical results and the histological findings proved that Ultram induced neuronal lesions could be mediated by the elevated cerebrocortical serotonin level which gives serious alarms for reconsidering the rush towards the excessive use of ultram

Effects of Hypertonic (7%) Saline on Brain Injury in Experimental Escherichia coli Meningitis

We sought to know whether hypertonic (7%) saline (HTS) attenuates brain injury by improving cerebral perfusion pressure (CPP) and down-modulating acute inflammatory responses in experimental bacterial meningitis in the newborn piglet. Twenty-five newborn piglets were assorted into three groups: 6 in the control group (C), 10 in the meningitis group (M), and 9 in the meningitis with HTS infusion group (H). Meningitis was induced by intracisternal injection of 10(8) colony forming units of Escherichia coli in 100 microliter of saline. 10 mL/kg of HTS was given intravenously as a bolus 6 hr after induction of meningitis, thereafter the infusion rate was adjusted to maintain the serum sodium level between 150 and 160 mEq/L. HTS significantly attenuated meningitis-induced brain cell membrane disintegration and dysfunction, as indicated by increased lipid peroxidation products and decreased Na+, K+-ATPase activity in the cerebral cortex in M. HTS significantly attenuated acute inflammatory markers such as increased intracranial pressure, elevated lactate level and pleocytosis in the cerebrospinal fluid observed in M. Reduced CPP observed in M was also significantly improved with HTS infusion. These findings implicate some attenuation of the meningitis-induced alterations in cerebral cortical cell membrane structure and function with HTS, possibly by improving CPP and attenuating acute inflammatory responses.

Effect of alcohol on neurons of iso-cortex--a histomorphometric study.

Effect of chronic intake of alcohol and its subsequent withdrawal was studied in albino mice on the layers of neurons of the iso-cortex. Neuronal density per mm2 of section in different layers of iso-cortex was counted and compared in 3 groups of animals (control, ethanol fed and withdrawal). Qualitative changes on nissl granules of neurons and myelinated fibres were also studied. Mice fed with 10% ethanol v/v ad libitum for 6 months showed loss of nissl granules and nucleolus and discontinuity of nuclear membrane. Quantitatively, significant reduction in neuronal density (P<0.001) was observed in layers II+III IV and V neurons of iso-cortex. Withdrawal of ethanol for 2 months showed continued reduction of counts of neuronal density in layers II+III and V only whereas reversal of count was found significantly (P<0.001) in layer IV of iso-cortex. Qualitatively, only few neurons showed prominent nissl granules after withdrawal of ethanol. More afferent synaptic connection in layer IV may be suggested as probable factor helping relative replenishment of neuronal count after withdrawal of alcohol.

Supersensitivity of the cholinergic muscarinic system in the rat's brain is induced by high concentrations of Cu+2

Transition metals have been described as regulators of receptor's function. here, we studied the effects of chronic administration of Cu2+ or the Cu2+ chelator penicillamine (PA) on the functional and binding properties of the muscarinic receptors (MR) on selected areas of rat's brain. Groups of 10 Sprague-Dawley rats were treated daily, for 45 days with either 1) 1 mg/Kg CuSO4 (Cu2+), 2) 100 mg/Kg PA, or 3) saline solution. Double T-maze and motility cages were used for behavioral testing and the binding assays were performed using [3H]-QNB or [3H]-N-MSCP as MR's ligands. Cu2+ brain levels were measured in the cerebral cortex by atomic absorption spectrophotometer. Results showed that PA treated rats displayed a significant decrease of locomotor's activity (LA) and rearing behavior (RB), but a significant increases in memory efficiency (ME). Cu2+ treated rats displayed diminished RB with no significant changes in LA. Cu2+ treated rats displayed higher MR's density (Bmax) in cortex (C), striatum (S), and hippocampus (H). An increase in Bmax was also observed in PA treated rats, but only in C and S. Finally, Cu2+ tissue concentration was significantly higher in C of both Cu2+ and with PA treated animals. In conclusion, 45 days of Cu2+ or PA treatment induced brain hypercuprosis, which was associated with MR binding supersensitivity; however, change in ME was only observed in PA treated rats suggesting that might be still another factor in these experiments besides Cu2+ (i.e., Zn2+ or PA itself) involved in memory modulation.