Search Results (27)

Background/objectives: Common carotid artery occlusion can cause oxidant and inflammatory damage to the optic nerve. In this study, the effect of sunitinib was investigated, the antioxidant and anti-inflammatory properties of which have been previously reported and shown to be protective in I/R injury and in preventing bilateral optic nerve ischemia–reperfusion (I/R) injuries after unilateral common carotid artery ligation in rats. Methods: In this study, 18 Albino Wistar male rats were divided into SG (sham-operated), CCU (clamping and unclamping), and SCCU (sunitinib + clamping and unclamping) groups. One hour before the surgical procedures, sunitinib (25 mg/kg, oral) was given to SCCU rats. Anesthesia was induced with ketamine (60 mg/kg, ip) and sevoflurane. The right common carotid arteries of all rats were accessed under anesthesia. While the skin opened in SG rats was closed with sutures, the right common carotid arteries of CCU and SCCU rats were clipped, and an ischemia period was created for 10 min. Then, reperfusion (6 h) was achieved by unclipping. After euthanasia with ketamine (120 mg/kg, intraperitoneally), the right and left optic nerves of the rats were removed and examined biochemically and histopathologically. Results: Malondialdehyde, tumor necrosis factor α, interleukin-1β, and interleukin-6 were increased, and total glutathione levels had decreased in both ipsilateral and contralateral optic nerves (p < 0.05). These changes were more prominent on the ipsilateral side. Similarly, histopathological damage was observed to be more on the ipsilateral side (p < 0.05). Biochemical and histopathological changes were significantly suppressed in rats receiving sunitinib treatment (p < 0.05). Conclusions: Sunitinib may protect optic nerve tissue against I/R injury by reducing oxidative stress and inflammation. Full article

Background: Oenothera rosea L’Her Ex. Aiton, presenting antioxidant and anti-inflammatory activities, is traditionally used to treat bruises and headaches and as a healing agent. This study aimed to investigate whether its organic fraction (EAOr) has neuroprotective properties against neuroinflammation in the context of ischemia/reperfusion. Methods: The chemical composition of EAOr was determined using HPLC techniques, and its neuroprotective activities were evaluated in a common carotid-artery ligation model for the induction of ischemia/reperfusion (I/R). The animals were supplemented with EAOR for 15 days. On the last day, the animals were rested for one hour, following which the common carotid-artery ligation procedure was performed to induce I/R. The neurological deficit was evaluated at 24 h after I/R using Bederson’s scale, and the relative expression of inflammatory genes and structure of hippocampal neurons were analyzed at 48 h. Results: The chemical analysis revealed five major compounds in EAOr: gallic acid, rutin, ellagic acid, and glucoside and rhamnoside quercetin. EAOr prevented neurological deficit 24 h after I/R; led to the early activation of the AIF and GFAP genes; reduced Nfkb1, IL-1beta, Il-6 and Casp3 gene expression; and protected hippocampal neurons. Conclusions: Our findings demonstrate that EAOr contains polyphenol-type compounds, which could exert a therapeutic effect through the inhibition of neuroinflammation and neuronal death genes, thus maintaining hippocampal neurons. Full article

The temporary ligation of the common carotid artery is performed as an emergency aid in cases of guttural pouch mycosis. Its usefulness is put into perspective after an anatomical summary of arterial vascularization involving a guttural pouch. It helps to better understand the need for the cranial (cerebral) and caudal (cardiac) occlusion of an arterial rupture by embolization in order to achieve maximum success in preventing and treating an hemorrhage. Topical oxygen therapy used alone or in a multimodal approach with embolization surgery is performed to promote healing of the inflammatory and mycotic lesions observed when an individual is affected. In conclusion, this three-step therapeutic approach should enable the equine practitioner to better orient their decision tree when faced with this condition which, while rare, can be potentially fatal if poorly treated. Full article

Nitric oxide (NO) is involved in the pathogenesis of cerebral ischemic injury. Here, we investigated the effects of aging on NO production during cerebral ischemia-reperfusion (IR). Male Wister rats (WRs) were assigned to 12-month-old (older; n = 5) and 3-month-old (younger; n = 7) groups. Similarly, male spontaneous hypertensive rats (SHRs) were allocated to 12-month-old (older; n = 6) and 3-month-old (younger; n = 8) groups. After anesthesia, their NO production was monitored using in vivo microdialysis probes inserted into the left striatum and hippocampus. Forebrain cerebral IR injuries were produced via ligation of the bilateral common carotid arteries, followed by reperfusion. The change in the NO₃⁻ of the older rats in the SHR groups in the striatum was less compared to that of the younger rats before ischemia, during ischemia, and after reperfusion (p < 0.05). In the hippocampus, the change in the NO₃⁻ of the older rats in the SHR groups was lower compared to that of the younger rats after reperfusion (p < 0.05). There were no significant differences between the two WR groups. Our findings suggested that aging in SHRs affected NO production, especially in the striatum, before and during cerebral ischemia, and after reperfusion. Hypertension and aging may be important factors impacting NO production in brain IR injury. Full article

Indoleamine 2,3-dioxygenase (IDO) and the tryptophan–kynurenine pathway (TRP-KP) are upregulated in ageing and could be implicated in the pathogenesis of delirium. This study evaluated the role of IDO/KP in lipopolysaccharide (LPS)-induced delirium in an animal model of chronic cerebral hypoperfusion (CCH), a proposed model for delirium. CCH was induced by a permanent bilateral common carotid artery ligation (BCCAL) in Sprague Dawley rats to trigger chronic neuroinflammation-induced neurodegeneration. Eight weeks after permanent BCCAL, the rats were treated with a single systemic LPS. The rats were divided into three groups: (1) post-BCCAL rats treated with intraperitoneal (i.p.) saline, (2) post-BCCAL rats treated with i.p. LPS 100 μg/kg, and (3) sham-operated rats treated with i.p. LPS 100 μg/kg. Each group consisted of 10 male rats. To elucidate the LPS-induced delirium-like behaviour, natural and learned behaviour changes were assessed by a buried food test (BFT), open field test (OFT), and Y-maze test at 0, 24-, 48-, and 72 h after LPS treatment. Serum was collected after each session of behavioural assessment. The rats were euthanised after the last serum collection, and the hippocampi and cerebral cortex were collected. The TRP-KP neuroactive metabolites were measured in both serum and brain tissues using ELISA. Our data show that LPS treatment in CCH rats was associated with acute, transient, and fluctuated deficits in natural and learned behaviour, consistent with features of delirium. These behaviour deficits were mild compared to the sham-operated rats, which exhibited robust behaviour impairments. Additionally, heightened hippocampal IDO expression in the LPS-treated CCH rats was associated with reduced serum KP activity together with a decrease in the hippocampal quinolinic acid (QA) expression compared to the sham-operated rats, suggested for the presence of endotoxin tolerance through the immunomodulatory activity of IDO in the brain. These data provide new insight into the underlying mechanisms of delirium, and future studies should further explore the role of IDO modulation and its therapeutic potential in delirium. Full article

Apoe-deficient (Apoe^−/−) and Ldlr-deficient (Ldlr^−/−) mice are two common animal models of hypercholesterolemia and atherosclerosis. The two models differ in lipid and glucose metabolism and other mechanisms involved in atherogenesis. Here we examined atherosclerotic lesion formation in the two models with an atherosclerosis-resistant C3H/HeJ (C3H) background. 3-month-old C3H-Ldlr^−/− and C3H-Apoe^−/− mice developed minimal atherosclerotic lesions in the aortic root when fed a chow diet. After 12 weeks on a Western diet, C3H-Ldlr^−/− mice developed 3-fold larger lesions than C3H-Apoe^−/− mice in the aortic root (127,386 ± 13,439 vs. 41,542 ± 5075 μm²/section; p = 0.00028), but neither knockout formed any lesion in the carotid artery. After being ligated near its bifurcation, the common carotid artery developed intimal lesions in both knockouts 4 weeks after ligation, significantly larger in C3H-Ldlr^−/− than C3H-Apoe^−/− mice (68,721 ± 2706 vs. 47,472 ± 8146 μm²/section; p = 0.028). Compared to C3H-Apoe^−/− mice, C3H-Ldlr^−/− mice showed a 50% reduction in plasma MCP-1 levels, similar levels of malondialdehyde, an oxidative stress biomarker, on both chow and Western diets, but higher small dense LDL levels on the Western diet. These results suggest a more significant role for small dense LDL than inflammation and oxidative stress in the different susceptibility of the mouse models to atherosclerosis. Full article

Vascular dementia (VD) is the second most common dementia syndrome worldwide, and effective treatments are lacking. Gastrodia elata Blume (GEB) has been used in traditional Chinese herbal medicine for centuries to treat cognitive impairment, ischemic stroke, epilepsy, and dizziness. Gastrodin (p-hydroxymethylphenyl-b-D-glucopyranoside, Gas) and Gastrodigenin (p-hydroxybenzyl alcohol, HBA) are the main bioactive components of GEB. This study explored the effects of Gas and HBA on cognitive dysfunction in VD and their possible molecular mechanisms. The VD model was established by bilateral common carotid artery ligation (2-vessel occlusion, 2-VO) combined with an intraperitoneal injection of sodium nitroprusside solution. One week after modeling, Gas (25 and 50 mg/kg, i.g.) and HBA (25 and 50 mg/kg, i.g.) were administered orally for four weeks, and the efficacy was evaluated. A Morris water maze test and passive avoidance test were used to observe their cognitive function, and H&E staining and Nissl staining were used to observe the neuronal morphological changes; the expressions of Aβ1-42 and p-tau396 were detected by immunohistochemistry, and the changes in energy metabolism in the brain tissue of VD rats were analyzed by targeted quantitative metabolomics. Finally, a Hippocampus XF analyzer measured mitochondrial respiration in H₂O₂-treated HT-22 cells. Our study showed that Gas and HBA attenuated learning memory dysfunction and neuronal damage and reduced the accumulation of Aβ1-42, P-Tau396, and P-Tau217 proteins in the brain tissue. Furthermore, Gas and HBA improved energy metabolism disorders in rats, involving metabolic pathways such as glycolysis, tricarboxylic acid cycle, and the pentose phosphate pathway, and reducing oxidative damage-induced cellular mitochondrial dysfunction. The above results indicated that Gas and HBA may exert neuroprotective effects on VD by regulating energy metabolism and mitochondrial function. Full article

Impaired glucocorticoid signaling in diabetes mellitus and its relation to suppressed immune function and hyperglycemia during acute stroke has been shown to be detrimental. Therefore, the aim of this study was to examine the effect of glucocorticoid receptor (GCR) blockers in a type-2 diabetic mouse model following hypoxia–ischemia (HI). We induced stroke in diabetic db/db and non-diabetic db/+ mice by unilateral common carotid artery ligation followed by 20 min of HI. Mice were pretreated with RU-486, GCRII blocker (40 mg/kg), intraperitoneally, the day before, during stroke and post-HI. Blood and brain samples were collected at 24 h post-HI to measure blood glucose, corticosterone and infarct size. Similarly, another set of mice was pretreated with RU-486 + spironolactone, GCR1 blocker (25 mg/kg) subcutaneously for a week before inducing stroke and during recovery. Samples were collected at 48 h post-HI for various analyses. RU-486 treatment did not lower the blood glucose significantly, but RU-486 + spironolactone decreased the blood glucose in db/db mice post-HI. However, none of the treatment groups decreased the ischemia-induced serum corticosterone level or infarct size. This study suggests that even though GCR blockers improve hyperglycemia, they did not improve the infarct volume. Full article

Ceftriaxone (CTX) exerts a neuroprotective effect by decreasing glutamate excitotoxicity. We further studied the underlying mechanisms and effects of CTX early post-treatment on behavior in a cerebral hypoperfusion rats. The rats’ common carotid arteries (2VO) were permanently ligated. CTX was treated after ischemia. Biochemical studies were performed to assess antioxidative stress and inflammation. Behavioral and histological studies were then tested on the ninth week after vessel ligation. The 2VO rats showed learning and memory deficits as well as working memory impairments without any motor weakness. The treatment with CTX was found to attenuate white matter damage, MDA production, and interleukin 1 beta and tumor necrosis factor alpha production, mainly in the hippocampal area. Moreover, CTX treatment could increase the expression of glia and the glial glutamate transporters, and the neuronal glutamate transporter. Taken together, our data indicate the neuroprotective mechanisms of CTX involving the upregulation of glutamate transporters’ expression. This increased expression contributes to a reduction in glutamate excitotoxicity and oxidative stress as well as pro-inflammatory cytokine production, thus resulting in the protection of neurons and tissue from further damage. The present study highlights the mechanism of the effect of CTX treatment and of the underlying ischemia-induced neuronal damage. Full article

The aim of the present study was to longitudinally evaluate the differences in cerebral volume and cerebral blood flow (CBF) on the right and left sides in rats with neonatal hypoxic–ischemic encephalopathy (HIE) using magnetic resonance imaging and the Rice–Vannucci model. Unilateral ligation of the left common carotid artery was performed on 8-day-old rats, followed by mild (1 h, n = 6) or severe (2 h, n = 7) hypoxic exposure. T₂-weighted (T₂W) and CBF images were obtained at 1 h and 1, 3, and 7 days following the HI insult. The cerebral volume (V_lesion and V_control), CBF in both hemispheres (lesion and control sides), and asymmetry indices of the cerebral volume (AI_volume) and CBF (AI_CBF) were calculated for each group. Slight hyperintensities were noted in the lesion-side hemispheres on T₂W images at 1 h and 1 day in both groups, as were pronounced hyperintensities at days 3 and 7 in the severe group. AI_volume was positive (V_lesion > V_control) in the mild and severe groups until days 1 and 3, respectively, and changed to negative on days 3 and 7 in the mild and severe groups. These results suggest that the prolonged positive AI_volume prior to day 3 in the severe group was caused by long-term cell swelling following severe HI insult. Full article

Cerebral ischemia induces oxidative brain injury via increased oxidative stress. Epigallocatechin gallate (EGCG) exerts anti-oxidant, anti-inflammatory, and metal chelation effects through its active polyphenol constituent. This study investigates whether EGCG protection against cerebral ischemia-induced brain cortex injury occurs through modulating lipid peroxidation, antioxidant activity, the essential elements of selenium (Se), zinc (Zn), magnesium (Mg), copper (Cu), iron (Fe), and copper (Cu), Zn/Cu ratio, and the hazardous metal lead (Pb). Experimentally, assessment of the ligation group was performed by occlusion of the right common carotid artery and the right middle cerebral artery for 1 h. The prevention group was intraperitoneally injected with EGCG (50 mg/kg) once daily for 10 days before cerebral ischemia. The brain cortex tissues were homogenized and the supernatants were harvested for biochemical analysis. Results indicated that cerebral ischemia markedly decreased SOD, CAT, Mg, Zn, Se, and Zn/Cu ratio and increased malondialdehyde (MDA), Fe, Cu, and Pb in the ischemic brain cortex. Notably, pretreating rats with EGCG before ischemic injury significantly reversed these biochemical results. Our findings suggest that the neuroprotection of EGCG in the ischemic brain cortex during cerebral ischemia involves attenuating oxidative injury. Notably, this neuroprotective mechanism is associated with regulating lipid peroxidation, antioxidant activity, essential elements, Zn/Cu ratio, and hazardous metal Pb. Full article

Perinatal hypoxia-ischemia (HI) is a major cause of neonatal brain injury, leading to long-term neurological impairments. Medical nutrition can be rapidly implemented in the clinic, making it a viable intervention to improve neurodevelopment after injury. The omega-3 (n-3) fatty acids docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3), uridine monophosphate (UMP) and choline have previously been shown in rodents to synergistically enhance brain phospholipids, synaptic components and cognitive performance. The objective of this study was to test the efficacy of an experimental diet containing DHA, EPA, UMP, choline, iodide, zinc, and vitamin B12 in a mouse model of perinatal HI. Male and female C57Bl/6 mice received the experimental diet or an isocaloric control diet from birth. Hypoxic ischemic encephalopathy was induced on postnatal day 9 by ligation of the right common carotid artery and systemic hypoxia. To assess the effects of the experimental diet on long-term motor and cognitive outcome, mice were subjected to a behavioral test battery. Lesion size, neuroinflammation, brain fatty acids and phospholipids were analyzed at 15 weeks after HI. The experimental diet reduced lesion size and neuroinflammation specifically in males. In both sexes, brain n-3 fatty acids were increased after receiving the experimental diet. The experimental diet also improved novel object recognition, but no significant effects on motor performance were observed. Current data indicates that early life nutritional supplementation with a combination of DHA, EPA, UMP, choline, iodide, zinc, and vitamin B12 may provide neuroprotection after perinatal HI. Full article

The thromboembolic ischemia model is one of the most applicable for studying ischemic stroke in humans. The aim of this study was to develop a novel thromboembolic stroke model, allowing, by affordable tools, to reproduce cerebral infarction in rats. In the experimental group, the left common carotid artery, external carotid artery, and pterygopalatine branch of maxillary artery were ligated. A blood clot that was previously formed (during a 20 min period, in a catheter and syringe, by mixing with a thromboplastin solution and CaCl₂) was injected into the left internal carotid artery. After 10 min, the catheter was removed, and the incision was sutured. The neurological status of the animals was evaluated using a 20-point scale. Histological examination of brain tissue was performed 6, 24, 72 h, and 6 days post-stroke. All groups showed motor and behavioral disturbances 24 h after surgery, which persisted throughout the study period. A histological examination revealed necrotic foci of varying severity in the cortex and subcortical regions of the ipsilateral hemisphere, for all experimental groups. A decrease in the density of hippocampal pyramidal neurons was revealed. Compared with existing models, the proposed ischemic stroke model significantly reduces surgical time, does not require an expensive operating microscope, and consistently reproduces brain infarction in the area of the middle cerebral artery supply. Full article

Cerebral ischemia results in increased oxidative stress in the affected brain. Accumulating evidence suggests that quercetin possesses anti-oxidant and anti-inflammatory properties. The essential elements magnesium (Mg), zinc (Zn), selenium (Se), and transition metal iron (Fe), copper (Cu), and antioxidants superoxide dismutase (SOD) and catalase (CAT) are required for brain functions. This study investigates whether the neuroprotective effects of quercetin on the ipsilateral brain cortex involve altered levels of essential trace metals, the Cu/Zn ratio, and antioxidant activity. Rats were intraperitoneally administered quercetin (20 mg/kg) once daily for 10 days before ischemic surgery. Cerebral ischemia was induced by ligation of the right middle cerebral artery and the right common carotid artery for 1 h. The ipsilateral brain cortex was homogenized and the supernatant was collected for biochemical analysis. Results show that rats pretreated with quercetin before ischemia significantly increased Mg, Zn, Se, SOD, and CAT levels, while the malondialdehyde, Fe, Cu, and the Cu/Zn ratio clearly decreased as compared to the untreated ligation subject. Taken together, our findings suggest that the mechanisms underlying the neuroprotective effects of quercetin during cerebral ischemic injury involve the modulation of essential elements, transition metals, Cu/Zn ratio, and antioxidant activity. Full article

Cerebral ischemia is related to increased oxidative stress. Resveratrol displays anti-oxidant and anti-inflammatory properties. The transition elements iron (Fe) and copper (Cu) are indispensable for the brain but overload is deleterious to brain function. Aluminum (Al) and arsenic (As) are toxic metals that seriously threaten brain health. This study was conducted to elucidate the correlation of the neuroprotective mechanism of resveratrol to protect cerebral ischemic damage with modulation of the levels of lipid peroxidation, anti-oxidants, transition elements, and toxic metals. Experimentally, 20 mg/kg of resveratrol was given once daily for 10 days. The cerebral ischemic operation was performed via occlusion of the right common carotid artery together with the right middle cerebral artery for 60 min followed by homogenization of the brain cortex and collection of supernatants for biochemical analysis. In the ligation group, levels of malondialdehyde, Fe, Cu, Al, and As increased but those of the anti-oxidants superoxide dismutase and catalase decreased. Pretreating rats with resveratrol before ischemia significantly reversed these effects. Our findings highlight the association of overload of Fe, Cu, As, and Al with the pathophysiology of cerebral ischemia. In conclusion, resveratrol protects against cerebral ischemic injury via restraining lipid peroxidation, transition elements, and toxic metals, but increasing anti-oxidant activity. Full article