Acute Cerebral Ischemia In Rats Research Articles

Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms.

PurposeCatalpol is the main active component of Rehmannia glutinosa, which has a variety of pharmacological activities, including anti-inflammatory and anti-oxidative effects. This study investigates the feasibility of catalpol intranasal administration and its protective effect on acute cerebral ischemia in rats via anti-oxidative and anti-apoptotic mechanisms.Patients and MethodsThis study investigates the method of catalpol intranasal administration to evaluate the nasal mucosal toxicity, brain targeting and pharmacokinetics of catalpol. The protective effect of catalpol of intranasal administration on stroke-induced brain injury in rats and its mechanisms on oxidative stress pathway Nrf2/HO-1 and apoptosis were also investigated using middle cerebral artery occlusion (MCAO).ResultsThe results showed that catalpol intranasal administration was safe and feasible with no hemolysis, no bad effect on the maxillary ciliary movement of bullfrog. After intranasal administration, the brain targeting index (DTI) of catalpol was greater than 1, which indicated that catalpol had good brain targeting after intranasal administration. The bioavailability of catalpol administered intranasally was higher than that of in plasma. In MACO model, catalpol intranasal administration could significantly reduce cerebral infarction volume, neurological dysfunction and brain edema. In addition, catalpol intranasal administration can also reduce the brain cell’s occurrence of apoptosis, promote the expression of Bcl-2 protein and inhibit the expression of Bax protein, reduce oxidative stress damage via up-regulating expression of Nrf2 and HO-1, increasing the activities of SOD and decreasing the activities of MDA.ConclusionCollectively, catalpol intranasal administration has good safety, stability and brain targeting. It can effectively protect the brain injury of the rat model of acute cerebral ischemia and provide the possibility of drug administration in the acute stage of cerebral ischemia, especially before entering the hospital.

Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats

ObjectiveOur previous research showed that Naotaifang (a compound traditional Chinese herbal medicine) extract (NTE) has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia. In this study, we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4 (GPX4) and iron metabolism. MethodsWe established an acute brain injury model of middle cerebral artery occlusion (MCAO) in rats, in which we could observe the accumulation of iron in neurons, as detected by Perl’s staining. Using assay kits, we measured expression levels of ferroptosis biomarkers, such as iron, glutathione (GSH), reactive oxygen species (ROS) and malonaldehyde (MDA); further the expression levels of transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), solute carrier family 7 member 11 (SLC7A11) and GPX4 were determined using immunohistochemical analysis, real-time quantitative polymerase chain reaction and Western blot assays. ResultsWe found that treatment with NTE reduced the expression levels of TFR1 and DMT1, reduced ROS, MDA and iron accumulation and reduced neurobehavioral scores, relative to untreated MCAO rats. Treatment with NTE increased the expression levels of SLC7A11, GPX4 and GSH, and the number of Nissl bodies in the MCAO rats. ConclusionTaken together, our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.

EVALUATION OF THE CEREBROPROTECTIVE ACTIVITY OF NOOTROPICS IN COMBINATION WITH MELAXEN BY A MORPHOLOGICAL ANALYSIS USING A MODEL OF BRAIN ISCHEMIA IN RATS

The cerebroprotective activity of nootropics in combination with melaxen (melatonin containing drug) was investigated by a comprehensive morphological analysis using an experimental model of acute cerebral ischemia in rats. According to the obtained data, a preventive use of vinpocetine in combination with melaxen signifi cantly reduces the degree of lethality among experimental animals and the severity of ischemic brain damage. A suggestion is made about the potential feasibility of melatonin-containing drugs for increasing the effi cacy of neuroprotection in cerebral ischemia.

Neuroprotective effect of magnesium-L-sulfonate on focal cerebral ischemia in rats and its mechamism

Objective To investigate the effects of magnesium sulfate and magnesium L-sulfonate on the neurobehavioral response and the expression of induced nitric oxide synthase (iNOS) in neurons after acute cerebral ischemia in rats. Methods One hundred and twelve male Sprague-Dawley (SD) rats were double-blinded randomly divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, MgSO4 treatment group, L-MgT treatment group. Each group was further divided into 6 h, 12 h and 24 h subgroups according to the different detection time points.Rat MCAO models were produced following the Longa's method.And the Longa score, limb-placing test, rotarod test, and sticky tape test were performed to evaluate the neurological damage, autonomous movement and coordinate perception in the 24 h subgroup. At the end of the experiment, 2, 3, 5-triphenyltetrazolium chloride (TTC) was used to evaluate the area of cerebral infarction at 24 h reperfusion. Immunohistochemical staining was employed to determine the alterations in iNOS expression in neurons 6 h, 12 h and 24 h after reperfusion. Results In behavioral evaluation: Longa score: Normal performance was observed in sham-operated group. Compared with the MCAO group, the scores of MgSO4 treatment group(1.71±0.18) and L-MgT treatment group(1.14±0.14) were decreased(t=0.548, 3.873, all P<0.05), and the score of L-MgT treatment group was lower than that of the MgSO4 group(t=2.828, P<0.05). Limb symmetry score: There was no statistically significant difference between MgSO4 group and MCAO group, but there was a statistically significant difference between L-MgT group and MCAO group (t=7.071, P<0.05). The roding experiment: The time of MgSO4 group and the L-MgT group were significantly different from that of the MCAO group (t=9.588, 20.776, P<0.05), and the time of the L-MgT group was significantly higher than that of the MgSO4 group (t=4.983, P<0.05). The right limb strip removal experiment: The time of MgSO4 group and L-MgT group were statistically different from that of MCAO group (t=6.135, 5.825, P<0.05), and the time of L-MgT group was increased compared with that of MgSO4 group(t=4.507, P<0.05). TTC test: No infarction was formed in the sham group.Compared with MCAO group ((36.82±1.35)%), the cerebral infarction volume of MgSO4 group ((17.39±1.72)%) and L-MgT group ((10.81±1.35)%) significantly decreased, with statistically significant differences (t=8.874, 11.105, P<0.05). Compared with MgSO4 group, cerebral infarction volume in L-MgT group was significantly reduced, with statistical significance (t=2.593, P<0.05). HE staining: There was no statistically significant difference in cell morphology between MgSO4 group and MCAO group at each time point, but the cell morphology of L-MgT group was intact compared with that of MCAO group.INOS staining at 24 h: There was no statistically significant difference in the positive cell density between the MgSO4 group and the MCAO group, but the L-MgT group (cortex: (196.7±8.1); striatum: (153.3±3.8)) positive cell density was lower than that of the MCAO group (cortex: (375.0±6.7), striatum: (358.3±4.5)), and the difference was statistically significant (t=11.113, 36.231, P<0.05). Conclusion L-MgT may have a significantly protective effect on MCAO rats, and its mechanism may be related to the level of iNOS in neurons. Key words: Cerebral ischemia; Magnesium sulfate; Magnesium L-threonate; Neurological function; Inducible nitric oxide synthase; SD rats

NGF/FAK signal pathway is implicated in angiogenesis after acute cerebral ischemia in rats

Neurogenesis in the cerebral infarction after an ischemic event is important to the rehabilitation of patients. However, the mechanism of angiogenesis around cerebral ischemia is not clear. Our study designed to test whether the nerve growth factor (NGF)-P-focal adhesion kinase (FAK) signaling pathway for associations with angiogenesis plays a key role in post-acute cerebral ischemia of rats. Firstly, we implanted the Matrigel, a carrier of basement membrane matrix, into the abdominal skin of rats to identify the relevant components of the NGF-P-FAK signaling pathway related to angiogenesis. Secondly, we used a model established by ligation of the middle cerebral artery (MCA) to observe the effect of the same signal pathway on angiogenesis in the subventricular and subgranular zones of the dentate gyrus(SVG and SGZ). The results showed that the tissue scores was significantly increased by NGF. However, the tissue scores was signifcaintly decreased by FAK inhibitor TAE226. Furthermore, CD31 and α-SMA were significantly increased by NGF and were decreased by anti-NGF and TAE226 in Matrigel. The P-FAK protein expression in Matrigel was markedly increased by NGF and decreased by TAE226. In the SVZ and SVG of cerebral ischemia, the numbers of BrdU-positive cells were significantly increased by NGF and decreased by TAE226, respectively. Our findings suggest that the therapy targeting the NGF-P-FAK signaling pathway may be an option for patients suffering from cerebral ischemia.

Kudiezi injection mitigates myocardial injury induced by acute cerebral ischemia in rats

BackgroundKudiezi (KDZ) injection is commonly used in traditional Chinese medicine as treatment for cerebral infarction and angina pectoris. The present study investigated the therapeutic effects of KDZ injection on myocardial injury induced by acute cerebral ischemia and the possibly protective mechanisms.MethodsRats were divided into three groups: sham, 6h-ischemia, and KDZ treatment (KDZ). The neurological deficits were determined by the Garcia score. The cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and brain water content was also evaluated. Serum creatinine kinase (CK), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) activity, myocardial tissue malondialdehyde (MDA) levels, L-Glutathione (GSH) levels, and superoxide dismutase (SOD) activity as well as mitochondrial cytochrome c oxidase (COX) activity were determined. Mitochondrial COX I and COX III mRNA expressions of myocardial tissues were measured by RT-PCR.ResultsImpaired neurological function and brain edema were observed in the 6h-ischemia group. TTC staining showed that the 6h-ischemia group had larger infarct zones than the sham group. Myocardial ischemic changes (widened myocardial cell gap, cracks, and obvious edema) were detected in the 6h-ischemia group compared with the sham group, with elevated serum CK-MB activity and CK and LDH levels. Electrocardiography showed lower medium frequency (MF) and high frequency (HF) in the 6h-ischemia group compared with the sham group. In myocardial tissue, COX activity was elevated in the 6h-ischemia compared with the sham group, while SOD, GSH, and MDA levels, and COX I and COX III mRNA expressions remained unchanged. KDZ injection decreased neurological impairment, brain edema, gaps between cells, and infarct size. Compared with the 6h-ischemia group, it reduced serum CK-MB activity and CK and LDH levels, and MDA levels in myocardial tissue. KDZ significantly increased GSH levels, SOD activity, and mitochondria COX activity and the expression of COX I and COX III mRNA in myocardial tissue compared with the sham group.ConclusionKDZ injection had a protective effect against cerebral ischemia in rats. KDZ injection could also alleviate myocardial injury after acute cerebral ischemia in rats. The possible mechanisms involve the regulation of the oxidative stress/antioxidant capacity after cerebral ischemia.

Dynamic contrast-enhanced MRI in the evaluation of blood-brain barrier permeability following acute cerebral ischemia in rats

Objective To investigate the dynamic changes of blood-brain barrier(BBB) permeability after acute cerebral ischemia in rats with middle cerebral artery occlusion (MCAO) by dynamic contrast-enhanced(DCE)-MRI. Methods Sixty MCAO rat models were established by suture-occlusion method. All rats were divided randomly into twelve groups with different ischemia duration (3 hours, 6 hours, permanent) and reperfusion times (2, 6, 12 and 24 hours after reperfusion). Each group was examined by MRI at the time points. The BBB permeability parameters(Ktrans, Ve, Kep, rKtrans, rVe, rKep) were calculated by Siemens workstation and compared with Evans blue(EB) extravasation results. Multivariate analysis of variance (M-ANOVA), one-way analysis of variance (one-way ANOVA), Pearson analysis were respectively used to verify the influences of ischemia duration and reperfusion time on BBB permeability parameters, EB extravasation and relationships between parameters. Results In 3 hours and 6 hours ischemia duration groups, change of BBB permeability after reperfusion appeared biphasic. At 2 hours and 6 hours after reperfusion, BBB permeability increased, while rKtrans values and rVe values rose and rKep values dropped. BBB permeability decreased at 12 hours and increased again at 24 hours after reperfusion. The highest BBB permeability was observed at 6 hours after reperfusion. However, BBB permeability in permanent ischemia groups had uniphasic change, as its increase was rather mild as ischemia time went on. rKtrans values(1.99±0.79)were positively correlated with rVe values(2.88±1.78)(r=0.93, P<0.01) and negatively correlated with rKep values(0.66±0.21)(r=-0.84, P<0.01). The negative correlation between rVe values and rKep valueswas also significant(r=-0.80, P<0.01). EB extravasation results were consistent with MRI findings. Conclusions BBB permeability change was biphasic in reperfusion groups, while it was uniphasic in permanent ischemia groups. DCE-MRI may accurately reflect the changes of BBB permeability after acute cerebral ischemia. Both ischemic duration and reperfusion time had influences on BBB permeability. With prolongation of ischemic time, the duration of BBB permeability increase became shorter, BBB damage appeared earlier, with increased degree of ischemic damage. Key words: Blood brain barrier; Reperfusion injury; Infarction, middle cerebral artery; Magnetic resonance imging

Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs.

Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90-min period, either an anti-VEGF neutralizing antibody (RB-222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB-222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB-222 was more effective than a 5 µg dose of the antibody. In addition, RB-222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB-222 significantly repressed VEGF expression as well as decreased MMP-2 and MMP-9 expression. However, it enhanced occludin and collagen-IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.

Abstract W P106: Pericyte Protection by Edaravone After Tpa Treatment in Rat Cerebral Ischemia

i) Background &amp; Objectives: Pericytes play a pivotal role in contraction, mediating inflammation, and regulation of blood flow in the brain. In the present study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. ii) Methods: Immunohistochemistry and Western blot analyses showed that the overlap between PDGFRβ-positive pericytes and N-acetylglucosamine oligomers (NAGO)-positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). iii) Results: The number of pericytes and the overlap with NAGO decreased with tPA, but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treatment damaged pericytes resulting in the detachment from astrocytes and a decrease in GDNF secretion. However, treatment with edaravone greatly improved tPA-induced damage to pericytes. iv) Conclusion: The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can extremely ameliorate such damage after acute cerebral ischemia in rats.

Pericyte protection by edaravone after tissue plasminogen activator treatment in rat cerebral ischemia.

Pericytes play a pivotal role in contraction, mediating inflammation and regulation of blood flow in the brain. In this study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. Immunohistochemistry and Western blot analyses showed that the overlap between platelet-derived growth factor receptor β-positive pericytes and N-acetylglucosamine oligomers (NAGO)-positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). The number of pericytes and the overlap with NAGO decreased with tPA but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treatment damaged pericytes, resulting in the detachment from astrocytes and a decrease in glial cell line-derived neurotrophic factor secretion. However, treatment with edaravone greatly improved tPA-induced damage to pericytes. The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can greatly ameliorate such damage after acute cerebral ischemia in rats. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Functional connectivity analysis of super acute cerebral ischemia in rats: a resting-state functional MRI empirical study

To investigate the change of low-frequency blood-oxygenation-level-dependent fluctuation (LFBF) after cerebral ischemia by functional connectivity analysis in the resting state. Super acute stroke rat-models with middle cerebral artery occlusion (MCAO) were employed in this study. Spontaneous fluctuations were recorded using a series of gradient-recalled echo-planar imaging (EPI) images before creation of the MCAO, and the same scan protocols were duplicated at the time of 60 min, 2 h after creation of the MCAO. FMRI signal time series from the different ROIs of ischemic cortex and normal cortex were preprocessed and low pass filtered. After preprocessing, the serial fMRI data was obtained by fast Fourier transformation to calculate the amplitude of the low-frequency fluctuations. Meanwhile, time course signal changes from a seed voxel of normal cortex were correlated with every voxel in the brain. Statistical analysis was performed across all rats to determine the extent of spatial correlation between regions. The amplitude of LFBF in the ischemic cortex between 0.01 and 0.1 Hz was lightly decreased during the super acute ischemic stroke. Howerever, the amplitude of LFBF in contralateral cortex was increased after 2 hours. Spatial distribution of LFBF, from cross-correlation analysis, indicates that the substantial inter-hemispheric synchrony of ischemic region was decreased and of contralateral cortex was enhanced during the super acute ischemic stroke. The contrast behavior of the resting state BOLD signal fluctuations and a intra-hemispheric symmetry in the LFBF with similar phase characteristics in most other regions during super acute ischemic stroke can be implied a new approach to detect the physiological activity functions and the distinct resting neural networks after the acute ischemic stroke takes place.

Correlating Tissue Outcome with Quantitative Multiparametric MRI of Acute Cerebral Ischemia in Rats

Predicting tissue outcome remains a challenge for stroke magnetic resonance imaging (MRI). In this study, we have acquired multiparametric MRI data sets (including absolute T(1), T(2), diffusion, T(1rho) using continuous wave and adiabatic pulse approaches, cerebral blood flow (CBF), and amide proton transfer ratio (APTR) images) during and after 65 mins of middle cerebral artery occlusion (MCAo) in rats. The MRI scans were repeated 24 h after MCAo, when the animals were killed for quantitative histology. Magnetic resonance imaging parameters acquired at three acute time points were correlated with regionally matching cell count at 24 h. The results emphasize differences in the temporal profile of individual MRI contrasts during MCAo and especially during early reperfusion, and suggest that complementary information from CBF and tissue damage can be obtained with appropriate MRI contrasts. The data show that by using three to four MRI parameters, sensitive to both hemodynamic changes and different aspects of parenchymal changes, the fate of the tissue can be predicted with increased correlation compared with single-parameter techniques. Combined multiparametric MRI data and multiparametric analysis may provide an excellent tool for preclinical testing of new treatments and also has the potential to facilitate decision-making in the management of acute stroke patients.

Fibrinolytic Effects of Transparietal Ultrasound Associated with Intravenous Infusion of an Ultrasound Contrast Agent: Study of a Rat Model of Acute Cerebral Stroke

The aim of this study was to evaluate the thrombolytic effect of focused transparietal ultrasound in combination with a specific contrast agent (microbubbles) in acute cerebral ischemia. Acute cerebral ischemia was induced in 10 rats by intra-arterial clots injection. Five rats (group 1) were treated with a combination of transparietal ultrasound (probe 2 MHz, acoustic power 500 mW/cm 2) and intravenous injection of 0.6 mL of the ultrasound contrast agent (UCA) sulfur hexafluoride. Five rats (group 2) were treated by fibrinolytic intravenous infusion (recombinant tissue plasminogen activator). Cerebral cellular energy production was determined by measuring the cellular phosphorylation using phosphorus magnetic spectroscopy before and during ischemia induction and after treatment. Measures were performed on a dedicated 2.35T magnet. The ratio phosphocreatine (P Cr) on inorganic phosphate (P i), P Cr/P i, estimation of the oxidative phosphorylation metabolism and the intracellular pH (pHi) were measured in the two groups. Compared with the ischemia induction period, both treatments were associated with an increase of P Cr/P i and pHi values, respectively, +80% and +100% in group 1 ( p = 0.07) and +100% and +80% in group 2 ( p = 0.04). There was no significant difference between the two groups for the response treatment. To conclude, treatment with intravenous fibrinolytic infusion and treatment with focused ultrasound in combination with UCA seems to be equally effective in treating acute cerebral ischemia in rats. (E-mail: j.p.tasu@chu-poitiers.fr)

Plasma and Brain Matrix Metalloproteinase-9 After Acute Focal Cerebral Ischemia in Rats

Plasma levels of matrix metalloproteinase-9 (MMP-9) have been proposed to be a useful biomarker for assessing pathological events in brain. Here, we examined the temporal profiles of MMP-9 in blood and brain using a rat model of acute focal cerebral ischemia. Plasma and brain levels of MMP-2 and MMP-9 were quantified at 3, 6, 12, and 24 hours after permanent middle cerebral artery occlusion in male Sprague-Dawley rats. Infarct volumes at 24 hours were confirmed with 2,3,5-triphenyl-tetrazolium-chloride staining. In plasma, zymographic bands were detected between 70 and 95 kDa corresponding to pro-MMP-2, pro-MMP-9, and activated MMP-9. A higher 135-kDa band was also seen that is likely to be NGAL-conjugated MMP-9. After ischemia, there were no significant changes in pro-MMP-2, but plasma levels of pro-MMP-9 steadily increased over the course of 24 hours. Activated MMP-9 levels in plasma were significantly elevated only at 24 hours. Plasma NGAL-MMP-9 complexes showed a transient elevation between 3 to 6 hours, after which levels decreased back down to pre-ischemic baselines. In brain homogenates, pro-MMP-2, pro-MMP-9, and activated MMP-9 were seen but no NGAL-MMP-9 bands were detected. Compared to the contralateral hemisphere, MMP-2 and MMP-9 levels in ischemic brain progressively increased over the course of 24 hours. Overall levels of MMP-9 in plasma and brain were significantly correlated, especially at 24 hours. Plasma levels of pro-MMP-9 at 24 hours were correlated with final infarct volumes. Elevated plasma levels of MMP-9 appear to be correlated with brain levels within 24 hours of acute cerebral ischemia in rats. Further investigation into clinical profiles of MMP-9 in acute stroke patients may be useful.

Arterial baroreflex function is an important determinant of acute cerebral ischemia in rats with middle cerebral artery occlusion

Aims To clarify whether arterial baroreflex function is an important determinant of acute cerebral ischemia in rats. Main methods Three animal models were used in this study. In the first, saponin conjugated with substance P (SP-SAP) was injected into the nucleus tractus solitarii (NTS) of Sprague–Dawley (SD) rats to block the central baroreflex arc. In the second model, sinoaortic denervation (SAD) was performed to destroy the peripheral baroreflex arc in SD rats. In the third model, SD rats were divided into two groups according to their naturally occurring BRS values. After determining hemodynamic indexes and baroreflex sensitivity (BRS), we subjected the animals to middle cerebral artery (MCA) occlusion. Levels of interleukin (IL)-1β and IL-6 were detected both in SAD/sham operation groups and low/high BRS groups. Key findings In all three animal models, baroreflex dysfunction significantly increased the infarct volume and weight. The levels of inflammatory factors were markedly elevated in SAD and low BRS groups. Significance These results demonstrate that the function of arterial baroreflex is an important determinant of acute cerebral ischemia in rats with MCA occlusion. Inflammation might be an important mechanism for the arterial baroreflex dysfunction-induced increase in brain damage in rats with MCA occlusion.

Behavioral and Histologic Neuroprotection of Aqueous Garlic Extract After Reversible Focal Cerebral Ischemia

The objective of the present study was to investigate the effects of aqueous garlic extract (AGE) on neurobehavioral activities, malondialdehyde (MDA) and reduced glutathione (GSH) levels, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and sodium-potassium ATPase (Na(+),K(+)-ATPase) activities, and glutamate and aspartate content in a middle cerebral artery (MCA) occlusion (MCAO) model of acute cerebral ischemia in rats. The right MCA of male Wistar rats was occluded for 2 hours using intraluminal 4-0 monofilament, and reperfusion was allowed for 22 hours. MCAO caused significant depletion in GSH and its dependent enzymes (GPx, GR, and GST) and significant elevation of MDA, glutamate, and aspartate. The activities of Na(+),K(+)- ATPase, SOD, and CAT were decreased significantly by MCAO. The neurobehavioral activities (grip strength, spontaneous motor activity, and motor coordination) were also decreased significantly in the MCAO group. All of the alterations induced by ischemia were significantly attenuated by pretreatment with AGE (500 mg/mL/kg of body weight, i.p.) 30 minutes before the induction of MCAO and correlated well with histopathology by decreasing the neuronal cell death following MCAO and reperfusion. These findings suggest that AGE effectively modulates neurobehavioral and neurochemical changes in focal ischemia, most probably by virtue of its antioxidant properties.

Effect of Saffron (Crocus sativus) on Neurobehavioral and Neurochemical Changes in Cerebral Ischemia in Rats

The modifying effects of Crocus sativus (CS) stigma extract on neurobehavioral activities, malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase (SOD), catalase (CAT), and Na(+),K(+)-ATPase activities, and glutamate (Glu) and aspartate (Asp) content were examined in the middle cerebral artery (MCA) occlusion (MCAO) model of acute cerebral ischemia in rats. The right MCA of male Wistar rats was occluded for 2 hours using intraluminal 4-0 monofilament, and reperfusion was allowed for 22 hours. MCAO caused significant depletion in the contents of GSH and its dependent enzymes while significant elevation of MDA, Glu, and Asp. The activities of Na(+),K(+)-ATPase, SOD, and CAT were decreased significantly by MCAO. The neurobehavioral activities (grip strength, spontaneous motor activity, and motor coordination) were also decreased significantly in the MCAO group. All the alterations induced by ischemia were significantly attenuated by pretreatment of CS (100 mg/kg of body weight, p.o.) 7 days before the induction of MCAO and correlated well with histopathology by decreasing the neuronal cell death following MCAO and reperfusion. The present results may suggest the effectiveness of CS in focal ischemia most probably by virtue of its antioxidant property.

Decompressive craniectomy in acute cerebral ischemia in rats: Is there any benefit in smaller thromboembolic infarcts?

Early craniectomy has shown to reduce infarction size in experimental large MCA infarction probably due to improved leptomeningeal perfusion. Based on the hypothesis that craniectomy may also be beneficial in smaller MCA infarction we evaluated the effects of craniectomy on infarction size in small thromboembolic cerebral infarction in rats. Therefore, thromboembolic cerebral ischemia was induced in 40 rats by endovascular injection of autologous, fibrin-rich emboli. Twenty-one animals with a diffusion-weighted MR imaging (DWI)-derived infarction size of 50–100 mm 3 (involving one- to two-third of the MCA territory) at 1 h after injection were randomly assigned to two groups. Eleven animals of group 1 immediately underwent craniectomy, ten animals of group 2 (controls) were not treated. Serial DWI was performed at 4 and 24 h. Infarction size was assessed by TTC-staining at 48 h after emboli injection. As result, prior to treatment, at 1 h after emboli injection, infarction size in groups 1 and 2 was 65.9 ± 16.0 mm 3 and 67.9 ± 17.8 mm 3, respectively. At 4 and 24 h, infarction size in group 1 was 73.5 ± 22.1 mm 3 and 85.2 ± 24.7 mm 3, and 76.3 ± 21.0 mm 3 and 83.4 ± 22.9 mm 3 in group 2, respectively. TTC-derived infarction size was 84.0 ± 23.3 mm 3 and 82.7 ± 21.5 mm 3, respectively. There was no significant difference between the two groups ( P > 0.79). In conclusion, our results demonstrate that for small thromboembolic MCA infarction early craniectomy is not beneficial.

Acute cerebral ischemia in rats studied by Carr-Purcell spin-echo magnetic resonance imaging: assessment of blood oxygenation level-dependent and tissue effects on the transverse relaxation.

Acute cerebral ischemia has been shown to be associated with an enhanced transverse relaxation rate in rat brain parenchyma, chiefly due to the blood oxygenation level-dependent (BOLD) effect. In this study, Carr-Purcell R(2) (CP R(2)), acquired both with short and long time intervals between centers of adiabatic pi-pulses (tau(CP)), was used to assess the contributions of BOLD and tissue effects to the transverse relaxation in two brain ischemia models of rat at 4.7 T. R(1rho) and diffusion MR images were also acquired in the same animals. During the first minutes of global ischemia, the long tau(CP) R(2) in brain parenchyma increased, whereas the short tau(CP) R(2) was unchanged. Based on the simulations, and using constraints of intravascular BOLD effect on parenchymal R(2), the former observation was ascribed to be due to susceptibility changes arising in the extravascular compartment. R(1rho) declined almost immediately after the onset of focal cerebral ischemia, and further declined during the evolution of ischemic damage. Interestingly, short tau(CP) CP R(2) started to decline after some 20 min of focal ischemia and declined over a time course similar to that of R(1rho), indicating that it may be an MRI marker for irreversible tissue changes in cerebral ischemia. The present results show that CP R(2) MRI can reveal both tissue- and blood-derived contrast changes in acute cerebral ischemia.

Protective effect of Nardostachys jatamansi in rat cerebral ischemia

The protective effect of Nardostachys jatamansi (NJ) on neurobehavioral activities, thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), thiol group, catalase and sodium–potassium ATPase activities was studied in middle cerebral artery (MCA) occlusion model of acute cerebral ischemia in rats. The right MCA of male Wistar rats was occluded for 2 h using intraluminal 4–0 monofilament and reperfusion was allowed for 22 h. MCA occlusion caused significant depletion in the contents of glutathione and thiol group and a significant elevation in the level of TBARS. The activities of Na +K + ATPase and catalase were decreased significantly by MCA occlusion. The neurobehavioral activities (spontaneous motor activity and motor coordination) were also decreased significantly in MCA occlusion group. All the alternations induced by ischemia were significantly attenuated by 15 days pretreatment of NJ (250 mg/kg po) and correlated well with histopathology by decreasing the neuronal cell death following MCA occlusion and reperfusion. The study provides first evidence of effectiveness of NJ in focal ischemia most probably by virtue of its antioxidant property.