Changes In Rat Brain Research Articles

Gynecological surgery in adulthood imparts cognitive and brain changes in rats: A focus on hysterectomy at short-, moderate-, and long-term intervals after surgery

Premenopausal hysterectomy is associated with a greater relative risk of dementia. We previously demonstrated cognitive impairments in adult rats six weeks after hysterectomy with ovarian conservation compared with intact sham-controls and other gynecological surgery variations. Here, we investigated whether hysterectomy-induced cognitive impairments are transient or persistent. Adult rats received sham-control, ovariectomy (Ovx), hysterectomy, or Ovx-hysterectomy surgery. Spatial working memory, reference memory, and anxiety-like behavior were tested either six-weeks post-surgery, in adulthood; seven-months post-surgery, in early middle-age; or twelve-months post-surgery, in late middle-age. Hysterectomy in adulthood yielded spatial working memory deficits at short-, moderate-, and long-term post-surgery intervals. Serum hormone levels did not differ between ovary-intact, but differed from Ovx, groups. Hysterectomy had no significant impact on healthy ovarian follicle or corpora lutea counts for any post-surgery timepoint compared with intact sham-controls. Frontal cortex, dorsal hippocampus, and entorhinal cortex were assessed for activity-dependent markers. In entorhinal cortex, there were alterations in FOSB and ΔFOSB expression during the early middle-age timepoint, and phosphorylated ERK1/2 levels at the adult timepoint. Collectively, results suggest a primary role for the uterus in regulating cognition, and that memory-related neural pathways may be modified following gynecological surgery. This is the first preclinical report of long-term effects of hysterectomy with and without ovarian conservation on cognition, endocrine, ovarian, and brain assessments, initiating a comprehensive framework of gynecological surgery effects. Translationally, findings underscore critical needs to decipher how gynecological surgeries, especially those involving the uterus, impact the brain and its functions, the ovaries, and overall aging from a systems perspective.

Understanding the role of zingerone on biochemical and behavioral changes in rat brain inflicted with C6 glioma cells.

Malignant glioma is the deadliest form of brain cancer. Zingerone (ZO), a polyphenolic compound found in ginger, offers pharmacological properties that make it a promising agent for containing the growth of glioma cells. The present study was conducted to understand the efficacy of ZO in containing the growth of C6 glioma cells. The study also assessed the prophylactic role of ZO on rat brain glioma induced by C6 cell lines by addressing its antioxidative action on biochemical, behavioral, and histoarchitectural indices. For dose optimization, the animals were pretreated with different doses of ZO for a period of 2 weeks before the inoculation of glioma cells (1 × 105 /10 µL phosphate-buffered saline) in the caudate region of rat brain and the treatment with ZO continued for 4 more weeks post implantation. In vitro studies were done to assess the radical scavenging activity of ZO and also to determine its effects on viability of C6 glioma cells at different concentrations. Glioma-bearing rats showed significant alterations in memory; exploratory and muscular activities which were appreciably improved upon simultaneous supplementation of ZOadministered at a dose of 50 mg/kg body weight and were also visible even at a higher dose. Glioma-bearing rats revealed a significant increase in reactive oxygen species, protein carbonyl contents, and lipid peroxidation, but showed a significant decrease in reduced glutathione and antioxidative enzymes in the brain tissue. Interestingly, all the biochemical indices and altered brain histoarchitecture displaying cellular atypia and hyperplasia showed appreciable improvement when supplemented with ZO at a dose of 50 mg/kg body weight.

A combined X-ray fluorescence and infrared microspectroscopy study for new insights into elemental-biomolecular obesity-induced changes in rat brain structures

The objective of our research was to determine the brain changes at the molecular and elemental levels typical of early-stage obesity. Therefore a combined approach using Fourier transform infrared micro-spectroscopy (FTIR-MS) and synchrotron radiation induced X-ray fluorescence (SRXRF) was introduced to evaluate some brain macromolecular and elemental parameters in high-calorie diet (HCD)- induced obese rats (OB, n = 6) and in their lean counterparts (L, n = 6). A HCD was found to alter the lipid- and protein- related structure and elemental composition of the certain brain areas important for energy homeostasis. The increased lipid unsaturation in the frontal cortex and ventral tegmental area, the increased fatty acyl chain length in the lateral hypothalamus and substantia nigra as well as the decreased both protein α helix to protein β- sheet ratio and the percentage fraction of β-turns and β-sheets in the nucleus accumbens were revealed in the OB group reflecting obesity-related brain biomolecular aberrations. In addition, the certain brain elements including P, K and Ca were found to differentiate the lean and obese groups at the best extent. We can conclude that HCD-induced obesity triggers lipid- and protein- related structural changes as well as elemental redistribution within various brain structures important for energy homeostasis. In addition, an approach applying combined X-ray and infrared spectroscopy was shown to be a reliable tool for identifying elemental-biomolecular rat brain changes for better understanding the interplay between the chemical and structural processes involved in appetite control.

Ameliorative Effect of Palm Oil in Aluminum Lactate Induced Biochemical and Histological Implications in Rat Brain.

α-Tocotrienol is one of the major constituents of palm oil. It is a well-known antioxidant and cholesterol-lowering neuroprotectant. To prevent the initiation of Alzheimer's like symptoms, much attention has been shifted to the major role played by antioxidants. Previous epidemiological reports correlate the increasing incidence of developing Alzheimer's disease (AD), to the aluminum (Al) content in drinking water. Al, being a ubiquitous element, has a long history of being particularly reactive towards multiple aspects of neurobiology. So, the current study examines the effect of Al-induced behavioral, biochemical, and histopathological changes in rat brain; and the ameliorative effect of palm oil in reducing the resulting neurotoxicity. The experimental design consisted of 4 groups: control group which received rodent chow diet and water ad libitum; Al group received aluminum lactate (50mg/kg bw); Al + palm oil group was administered with Al (50mg/kg bw) and palm oil (60mg/kg bw); and palm oil group received palm oil (60mg/kg bw). Al was given by oral gavage once daily for 6weeks and palm oil was administered intraperitoneally. After 6weeks of supplementation, Al + palm oil group showed significantly lower malondialdehyde (MDA) content, but higher superoxide dismutase (SOD), catalase (CAT), GST, and GPx activity as compared to Al group. Al group has significantly higher level of MDA content, but lower SOD, CAT, GST, and GPx activity as compared to control group. In conclusion, this study suggested that palm oil was effective in preventing the Al-induced brain damage in rats.

An imbalance between RAGE/MR/HMGB1 and ATP1α3 is associated with inflammatory changes in rat brain harboring cerebral aneurysms prone to rupture

Background and purposeAn aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na+/K+-ATPase (ATP1α3).MethodsTen-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet.ResultsSix weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05).ConclusionsRegulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.

N-acetylcysteine protects against cuprizone-induced demyelination: histological and immunohistochemical study.

Myelination is a sequential process that is tightly controlled by a number of intrinsic and extrinsic factors. Any central nervous system disease in which the neuronal myelin sheath is damaged is referred to as demyelinating disease. The present work was designed to study the histopathological, ultrastructural and immunohistochemical changes in rat brain, mainly corpus callosum (CC), following oral administration of cuprizone (CPZ), and the role of N-acetylcysteine (NAC) in reducing these changes. Demyelination was induced by CPZ administration for short (4 weeks) and long (8 weeks) periods. NAC was given concomitantly and sequentially for similar periods. Spontaneous recovery after cessation of CPZ followed by no medication was also investigated. At the end of each experimental period, both cerebral hemispheres were extracted and prepared for light and electron microscopic examination and immuno-histochemical study. The obtained results showed a direct proportion between the duration of CPZ administration and the severity of demyelination. The co-administration of CPZ and NAC, had a fair protective impact that was stronger than the sequential administration of the two drugs. Incomplete spontaneous remyelination was observed after cessation of CPZ, being more evident in short than in long period group, indicating that when CPZ administration is prolonged, remyelination is delayed. In the light of the above results, it could be concluded that NAC has neuroprotective effects and has the potential to be a novel therapeutic approach for the treatment of demyelinating diseases such as multiple sclerosis; however, treatment should begin as soon as the disease manifests.

Streptozotocin‐induced sporadic Alzheimer's disease: Behavioral effects in female rats

Sporadic Alzheimer's disease (SAD) is the main cause of dementia worldwide with no effective therapy. This multifactorial pathology is characterized by behavioral and cognitive impairment. Despite the fact that women show an increased risk of SAD, female animals are often excluded from basic research. In this line, an intracerebroventricular infusion of streptozotocin (icv-STZ) is commonly employed to generate SAD model in male animals. However, whether sex differences exist in the icv-STZ model remains unknown. Our objective was to study the female brain changes in rats with experimental SAD. Animals were submitted into 4 experimental groups (female Sprague Dawley rats, N=8): Sham, STZ, OVX and OVX+STZ. OVX and OVX+STZ groups were ovariectomized and, 14 days later, STZ and OVX+STZ groups were injected with 3 mg/kg icv-STZ. Body weight of all rats was registered along the experiment every week. During the last two weeks until the end of the study (day 30 post icv-STZ), we assessed several behavioural tests: species-typical behaviour (Marble Burying), object recognition memory (Novel Object Recognition), spatial learning and memory (Barnes Maze), and depressive-like behaviour (Forced Swim Test). Our preliminary results show that STZ affected behavioral performance differently in the SAD model depending on the ovarian steroid levels of female rats. Overall, we conclude that the potential impact of sex differences on brain function is a relevant issue and it should be considered in future SAD research.

Diffusion kurtosis imaging: An efficient tool for evaluating age-related changes in rat brains.

PurposeTo evaluate and determine age‐related changes in rat brains by studying the diffusion kurtosis imaging results among different age groups of rats.MethodsSprague–Dawley (SD) rats underwent conventional magnetic resonance imaging (MRI) and diffusion Kurtosis Imaging (DKI). Two diffusion values of mean kurtosis (MK) and kurtosis (K⊥) were measured and analyzed based on laterality, brain regions and age groups. The MK and K⊥ data were plotted against different age groups.ResultsNo laterality was found for the MK or K⊥ values in the cerebral cortex (CT), external capsule (EC), or caudate putamen (CPu) regions. In contrast, significant changes in these values were observed among different age groups. Changes of the MK and K⊥ values were significant in both hemispheres in the EC, the CT, and the CPu brain regions. The changes in the MK and K⊥ values showed a parabolic relationship with ages in all the brain regions.ConclusionNo laterality in the MK and K⊥ values was observed for the EC, CT, or CPu regions of the rat brain. Significant changes in MK and K⊥ values were both observed among different age groups, thus suggesting diffusion kurtosis imaging as an efficient tool for studying brain aging in rats.

Blood–brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses

Intracarotid arterial hyperosmolar mannitol (ICAHM) blood-brain barrier disruption (BBBD) is effective and safe for delivery of therapeutics for central nervous system malignancies. ICAHM osmotically alters endothelial cells and tight junction integrity to achieve BBBD. However, occurrence of neuroinflammation following hemispheric BBBD by ICAHM remains unknown. Temporal proteomic changes in rat brains following ICAHM included increased damage-associated molecular patterns, cytokines, chemokines, trophic factors, and cell adhesion molecules, indicative of a sterile inflammatory response (SIR). Proteomic changes occurred within 5 min of ICAHM infusion and returned to baseline by 96 h. Transcriptomic analyses following ICAHM BBBD further supported an SIR. Immunohistochemistry revealed activated astrocytes, microglia, and macrophages. Moreover, proinflammatory proteins were elevated in serum, and proteomic and histological findings from the contralateral hemisphere demonstrated a less pronounced SIR, suggesting neuroinflammation beyond regions of ICAHM infusion. Collectively, these results demonstrate ICAHM induces a transient SIR that could potentially be harnessed for neuroimmunomodulation.

Evaluation of mobile phone radiation-induced structural changes of rat brain with emphasis on the possible protective role of pomegranate peel extract

Evaluation of mobile phone radiation-induced structural changes of rat brain with emphasis on the possible protective role of pomegranate peel extract

Evaluation of mobile phone radiation-induced structural changes of rat brain with emphasis on the possible protective role of pomegranate peel extract

Evaluation of mobile phone radiation-induced structural changes of rat brain with emphasis on the possible protective role of pomegranate peel extract

Effect of alpha-cypermethrin on serotonin, nor-epinephrine and brain changes in rats

In the present study, brain damages, serotonin and nor-epinephrine activity on rat brain were investigated. A single sub-acute lethal -oral dose of Alpha-Cypermethrin (25 mg kg -1) was given to rat. Blood and brain tissue samples were examined biologically and histopathologically at various times (1, 2, 3, 4 and24 h) after dosing. Results revealed that extracellular serotonin levels % (f mol/mg tissue) in rat ventral hippocampus at 25 mg kg-1 B.W. After 1, 2, 3 and 24 hr. were 105±4, 80 ±7, 80 ±4, 70 ±4, respectively. While extracellular NA levels after 1, 2, 3 and 24 hr. were 300±10, 450 ±14, 400±12, 400±11, respectively. Alpha-cypermethrin acts as nor-epinephrine reuptake inhibitors (NRIs) and serotonin reuptake stimulator in rat brain. The lesions in the brain of the treated groups were gliosis, perineuronal vacuolation, perivascular vacuolation, and neuronal degeneration.

Investigation of Early Death-Induced Changes in Rat Brain by Solid Phase Microextraction via Untargeted High Resolution Mass Spectrometry: In Vivo versus Postmortem Comparative Study.

Analysis of brain samples obtained postmortem remains a standard approach in neuroscience, despite often being suboptimal for inferring roles of small molecules in the pathophysiology of brain diseases. Sample collection and preservation further hinders conclusive interpretation of biomarker analysis in autopsy samples. We investigate purely death-induced changes affecting rat hippocampus in the first hour of postmortem interval (PMI) by means of untargeted liquid chromatography-mass spectrometry-based metabolomics. The unique possibility of sampling the same brain area of each animal both in vivo and postmortem was enabled by employing solid phase microextraction (SPME) probes. Four millimeter probes coated with mixed mode extraction phase were used to sample awake, freely roaming animals, with 2 more sampling events performed after death. Significant changes in brain neurochemistry were found to occur as soon as 30 min after death, further progressing with increasing PMI, evidenced by relative changes in levels of metabolites and lipids. These included species from several distinct groups, which can be classified as engaged in energy metabolism-related processes, signal transduction, neurotransmission, or inflammatory response. Additionally, we perform thorough analysis of interindividual variability in response to death, which provides insights into how this aspect can obscure conclusions drawn from an untargeted study at single metabolite and pathway level. The results suggest high demand for systematic studies examining the PMI time course with in vivo sampling as a starting point to eliminate artifacts in the form of neurochemical changes assumed to occur in vivo.

Valproate Limits Vascular Remodeling and Protects Against Memory Deficits Following Chronic Hypoperfusion

Background and PurposeChronic cerebral hypoperfusion is a risk factor for vascular cognitive impairment. Bilateral carotid artery stenosis (BCAS), a physiologically relevant model of chronic cerebral hypoperfusion, produces damage to the deep white matter of the brain with corresponding deficits in working memory. BCAS increases histone deacetylase (HDAC) activity and global histone acetylation changes in rat brains which may play a role in smooth muscle cell phenotypic changes and vascular remodeling. We tested the hypothesis that treatment of BCAS rats with the HDAC inhibitor, valproate (VPA), limits remodeling and protect rats from memory deficits.MethodsTwenty female Sprague Dawley rats age 16–20 weeks old were subjected to either sham or BCAS surgery and treated with either 300 mg/kg/day VPA or vehicle for eight weeks. Cognitive function was assessed using the novel object recognition test. Rats were subjected to laser speckle imaging to determine cerebral blood flow and then euthanized. Gene expression of HDAC9, ACTA2 and Ki67was measured in the basilar artery using qPCR. All data are reported as the mean ± the standard error (n=5 per group). All experiments were analyzed using one‐way ANOVA with a Bonferoni correction. P‐values of less than 0.05 were considered significant.ResultsAs expected, there was no significant difference in cerebral perfusion between the sham‐vehicle and the BCAS‐vehicle groups at euthanasia. Furthermore, treatment of the rats with VPA had no effect on cerebral perfusion. HDAC expression in the basilar artery of BCAS‐vehicle rats was increased compared to sham‐vehicle rats (1.6 ± 0.2 vs. 1.0 ± 0.1, P=0.0161) and HDAC expression in BCAS‐VPA rats was restored to the sham‐vehicle treated levels (0.9 ± 0.1 vs. 1.0 ± 0.1). Increased ACTA2 expression is a marker for hypertrophy due to hemodynamic stress and was increased in the basilar artery of BCAS‐vehicle rats compared to sham‐vehicle rats (2.3± 0.8 vs. 1.0 ± 0.1, P=0.0494). While VPA had no effect on ACTA2 expression in the sham‐VPA rats, ACTA2 expression in the basilar arteries of BCAS‐VPA rats was restored to the sham‐vehicle levels (0.9 ± 0.3 vs. 1.0 ± 0.1). MKI67 expression was unchanged in BCAS‐vehicle compared to the sham‐vehicle rats while the proliferative marker was increased in the BCAS‐VPA treated rats compared to the sham‐vehicle (3.2 ± 0.7 vs. 1.5 ± 0.4, P=0.0409) and to the BCAS‐vehicle rats (3.2 ± 0.7 vs. 1.3 ± 0.3, P=0.0298). Novel object exploration tests indicate that BCAS‐vehicle rats explored the novel object 29.4 ± 7.1% less than sham‐vehicle rats (P=0.0186) while BCAS‐VPA rats appeared protected from memory impairment and explored the novel object the same amount as the sham‐vehicle rats.Conclusion and future directionsVPA treatment results in decreased expression of hypertrophic markers and is associated with functional restoration of working memory in BCAS rats with white matter injury caused by BCAS. There is a translational potential for clinically used HDAC inhibitors in the treatment of vascular cognitive impairment. Future work will focus on determining sex differences in the response to BCAS and treatment with VPA as well as quantifying white matter injury, and vessel density within the cortex.Support or Funding InformationThe Brain Aneurysm Foundation Research Award

Synchronous measuring of triptolide changes in rat brain and blood and its application to a comparative pharmacokinetic study in normal and Alzheimer’s disease rats

Triptolide, a major active ingredient of Tripterygium wilfordii Hook F, provides anti-inflammatory and neuroprotective activities. In this study, a microwave-assisted stable isotope labeling derivatization-magnetic dispersive solid phase extraction (MA-SILD-MDSPE) combined with ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been developed for the determination of the triptolide in rat microdialysates. A pair of SILD reagents (d0-/d3-3-N-methyl-2’-carboxyl Rhodamine 6G, d0-/d3-MCR6G) were used to label triptolide in real samples and standards under mild conditions. The introduction of SILD reagents enhanced the sensitivity of MS/MS detection and ensured accurate quantification. A novel molecularly imprinted polymer coating with d0-MCR6G labeled triptolide as template was firstly synthesized by precipitation polymerization method, and used to selectively extract the labeled triptolides from complex matrices. The purified d0-/d3-MCR6G-triptolides were determined by UHPLC-MS/MS analysis. Using the proposed method, a good linearity (R2>0.995), low limits of detection (LOD, 0.45–0.50 pg/mL) and quantification (LOQ, 3.0 pg/mL) were achieved. The intra- and inter-day precision and accuracy were within the acceptable ranges. No significant matrix effect was observed. The derivatization efficiency was more than 96 %. The validated method was successfully applied to a comparative pharmacokinetic study of triptolide synchronously in brain and blood of normal and Alzheimer’s disease rats by in vivo microdialysis sampling technique.

Responses of Immune Organs after Cerebral Ischemic Stroke.

Stroke is a leading cause of death and disability worldwide. Recently, secondary damage to the brain has been hypothesized as a key aggravating element in the ischemic cascade. However, the interaction between cerebral infarction and immune organs is not fully understood. In this study, we investigated changes in rat brain, spleen, thymus, mesenteric lymph node, and liver at 3, 7, and 13 days after transient middle cerebral artery occlusion (tMCAO) by immunohistochemistry. Rat models of stroke were made by tMCAO. Functional assessment was performed at 3 h and 1, 3, 5, 7, 9, 11, and 13 days after MCAO. Rat organs were harvested for 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry. The number of CD8α+ T cells decreased in spleen, thymus, mesenteric lymph node, and liver and increased in brain. Numbers of Iba1+ and CD68+ macrophages decreased in spleen, thymus, and mesenteric lymph node and increased in brain and liver. Ki67+ cells exhibited the same characteristics as macrophages, and increased numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) -positive apoptotic cells were present in spleen, mesenteric lymph node, liver, and brain. The present results indicate that stroke is a systemic disease that, in addition to affecting the brain, also induces responses in immune organs. These results suggest that systemic treatment might be a good strategy for clinical stroke care.

Role of quercetin and caloric restriction on the biomolecular composition of aged rat cerebral cortex: An FTIR study.

Aging brain is characterized by a change in biomolecular composition leading to a diverse range of neurological diseases. Anti-aging research is of current interest, to lessen the burden of age-related macromolecular damage through antioxidant supplementation and caloric restriction. However, data concerning the effect of these anti-aging regimens on age-related biomolecular changes in rat brain is still lacking. In the present study, for the first time, we employed Fourier transform infrared (FTIR) spectroscopy, to investigate the effect of quercetin, caloric restriction (CR) and combination of both on alterations in the composition of lipids and proteins of aged rat brain cerebral cortex. Aged male Wistar rats (21 months old) were divided into four groups: Control (CONT), fed pellet diet; Quercetin (QUER), fed quercetin (50 mg/kg/day); CR (caloric restriction) (fed 40% reduced CONT), and CRQ (40% CR and 50 mg/kg/day QUER). Three-month-old rats served as young control (YOUNG). Our short-term study (45 days) shows decreased band area of unsaturated lipids, decreased area ratios of olefinic/lipid and CH2 antisymmetric stretching (2925 cm-1)/lipids in CONT group compared to young rats, suggesting age-associated lipid peroxidation in aged rats. A slight decrease in the frequency of CH2 antisymmetric mode of lipids (whereas no change in CH2 symmetric mode), but a decrease in bandwidths of both CH2 antisymmetric and symmetric modes of lipids was observed for CONT group compared to YOUNG. Further, a significant decrease in the peak area of infrared bands of proteins and an increase in the peak area of the CO band of lipids was observed in the CONT group. Our data also show that lower levels of α-helical structures and higher levels of random coils, representing altered protein secondary structure composition in the CONT group compared to YOUNG group. Reduction in neuronal cell density and shrinked nucleus was also observed in aged rats. Increase in the accumulation of oxidative mediated damage to macromolecules and diminished antioxidant levels, could be the possible reason for the age-related alterations in the composition of lipids and proteins. However, the combination of quercetin and CR, but not either treatment alone, significantly prevented the age associated alterations in the lipid and protein profiles in the rat cerebral cortex. Further, our results help to understand the mechanism of action of antioxidants under non-restriction and CR conditions, this might help in the development of novel anti-aging treatments to ameliorate oxidative stress in age-related disorders.

Lipid metabolic changes in rat brain during permanent cerebral ischemia

Инсульт головного мозга является важнейшей проблемой современного человечества, миллионы людей ежегодно становятся жертвами этого недуга. Несмотря на масштабные исследования в этой области, до сих пор существует недостаток информации о патофизиологии ишемического инсульта. Тщательное изучение изменений биохимических показателей на раннем этапе заболевания позволит установить механизм его протекания и в будущем найти эффективное решение проблемы. Ключевая роль в патогенезе инсульта принадлежит липидам и молекулам, ассоциированным с их биосинтезом и поддержанием их функционального состояния. С одной стороны, при патогенезе инсульта происходит мощный окислительный стресс, который приводит к повреждению молекул, в том числе липидного состава. С другой стороны, из-за нехватки восстановительных эквивалентов останавливается биосинтез новых молекул взамен поврежденных. Целью работы было исследовать изменения в тканях мозга крыс при ишемии таких параметров, как концентрации общего холестерина, свободных жирных кислот (СЖК), малонового диальдегида (МДА), а также уровней восстановленного глутатиона (GSH) и общего НАДФ(Н). В результате исследования выявлено, что через 24 ч с момента начала развития ишемии уровни СЖК, холестерина и GSH существенно снижаются, при этом уровень МДА, маркера перекисного повреждения липидов, увеличивается. Уровень общего пула НАДФ(Н) снижается в 2 раза уже через 6 ч с момента окклюзии сосуда.

Changes of autophagy in brain tissue after asphyxial cardiac arrest and cardiopuimonary resuscitation

Objective To establish a simple rat model of asphyxia cardiac arrest (CA) by clamping endotracheal tube and observe the changes of autophagy after cardiopuimonary resuscitation (CPR). Methods A total of 30 clean male Sprague Dawley rats, weighing 200-300 g, were randomly divided into sham operation group (n=6) and CA/CPR group (n=24), then the CA/CPR group was subdivided into 4 subgroups: 3 h group, 6 h group, 24 h group and 72 h group after resuscation of spontaneous circulation (ROSC), with 6 rats in each group. Neurological deficit scores (NDS) were evaluated at different time points after ROSC. Morphological changes of rat brain were observed by hematoxylin and eosin (HE) staining. The expression of tubulin light chain 3 (LC3), Beclin-1 and Parkin in the hippocampus was detected by Western blotting. The immunofluorescence was used to observe the expression of LC3. Results Compared with the sham operation group, the NDS scores in the CA/CPR group were significantly reduced at each time point, and the brain tissue damage was significantly aggravated. The ratio of LC3Ⅱ/Ⅰ in the 6, 24 and 72 hsubgroups after ROSC was (0.443±0.058), (0.588±0.073), and (0.286±0.036), respectively. Compared with the sham operation group (0.127±0.386), the differences were statistically significant (P<0.01). The expression levels of Beclin-1 in the 6, 24 and72 hsubgroups after ROSC were (0.531±0.033), (0.640±0.039), and (0.435±0.036), respectively. Compared with the sham operation group (0.216±0.028), the expression levels were significantly higher (P<0.01). The expression levels of Parkin in the 6, 24 and 72 h subgroups after ROSC were (0.621±0.021), (0.706±0.020), and (0.588±0.014), respectively. Compared with the sham operation group (0.329±0.032), the expression levels were significantly higher. The difference was statistically significant (P<0.01). The average absorbance of the immunofluorescence in the CA/CPR group was (8.66±0.99)%, which was significantly higher than that in the sham operation group (3.87±0.62)% (P<0.01), suggesting that the proportion of LC3 particles in the CA/CPR group increased. Conclusion Five min of CA in rats causes significant damage to brain tissue. Autophagy (including mitophagy) was activated at 6 h after ROSC, which was the highest at 24 h, decreased at 72 h but was still activated by autophagy. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Autophagy; Mitophagy; Rat

Comparison of Neurotoxicity of L-Monosodium Glutamate and a Commercially Available Glutamate Salt in PC-12 cells

Comparison of Neurotoxicity of L-Monosodium Glutamate and a Commercially Available Glutamate Salt in PC-12 cells