The purpose of this study was to identify time-related changes in clinical, MRI, histopathologic, and immunohistochemical findings associated with ischemic stroke in dogs. Additionally, the association of cerebrospinal fluid (CSF) and tissue levels of interleukin (IL)-6 with clinical prognosis was assessed. Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO) in nine healthy experimental dogs. The dogs were divided into three groups according to survival time and duration of the experimental period: group A (survived only 1 day), group B (1-week experimental period), and group C (2-week experimental period). Neurologic status was evaluated daily. Magnetic resonance imaging (MRI) was performed according to a predetermined schedule. Concentration of IL-6 in CSF was measured serially after ischemic stroke. Postmortem examination was performed for all experimental dogs. During histopathological examination, variable degrees of cavitation and necrosis due to neuronal cytopathic effects, such as pyknotic nuclei and cytoplasmic shrinkage, were observed on the affected side of the cerebral cortex in all dogs. Immunohistochemistry specific for IL-6 showed increased expression in the ischemic lesions. CSF IL-6 concentrations and ischemic lesion volumes 1 day after ischemic stroke were significantly higher in group A compared to groups B and C.
Animals ; Brain Ischemia/*etiology ; Dogs ; Female ; *Immunohistochemistry ; *Infarction, Middle Cerebral Artery ; *Magnetic Resonance Imaging ; Male ; Stroke/*pathology

The aim of the present study was to assess the clinical and histopathological findings in a canine model of ischemic stroke. Cerebral ischemic stroke was induced by middle cerebral artery occlusion in four healthy beagle dogs using silicone plugs. They showed neurological signs of forebrain dysfunction such as reduced responsiveness, head turning, circling, postural reaction deficits, perceptual deficits, and hemianopsia. These signs gradually regressed within 4 weeks without therapy. On magnetic resonance imaging, T2 hyperintensity and T1 hypointensity were found in the cerebral cortex and basal ganglia. These lesions were well-defined and sharply demarcated from adjacent brain parenchyma with a homogenous appearance. No abnormalities of the cerebrospinal fluid were observed. At necropsy, atrophic and necrotic lesions were observed in the cerebral cortex. The cerebral cortex, basal ganglia, and thalamus were partially unstained with triphenyl-tetrazolium chloride. Histopathologically, typical features of infarction were identified in cortical and thalamic lesions. This study demonstrates that our canine model resembles the conditions of real stroke patients.
Animals ; Behavior, Animal/physiology ; Brain/metabolism/pathology ; Cerebral Infarction/*etiology/*pathology ; Cerebrospinal Fluid/chemistry/cytology ; Disease Models, Animal ; *Dogs ; Infarction, Middle Cerebral Artery/*complications/*pathology ; Magnetic Resonance Imaging ; Male

OBJECTIVETo observe the effects of Xuezhikang and simvastatin on cerebral ischemia/reperfusion injury in rat, as well as the influences after intervention with L-NAME.

METHODRats were given orally with Xuezhikang and simvastatin or vehicle for 2 weeks, and then subjected to middle cerebral artery occlusion for 120 min using intraluminal filament model. L-NAME were injected into the lateral ventricles in half of the rats treated with Xuezhikang and simvastatin 45 min before the ischemia. The neurological deficits examinations were performed at 2, 24, 48 h after reperfusion. After the last examination the animals were sacrificed, the infarct volumes were determined by TTC staining, and MDA levels were also measured.

RESULTXuezhikang and simvastatin both significantly reduced the infarct volume and improved the functional recovery when compared to vehicle. Xuezhikang and simvastatin both significantly decreased the MDA accumulation after reperfusion. L-NAME partially inhibited the protective effect of Xuezhikang but nearly completely abolished the protective effect of simvastatin.

CONCLUSIONXuezhikang has protective effects on ischemic brain damage in rats, which the beneficial effects are partly due to the statins components. The other components in Xuezhikang may also account for the neuroprotective effects, which is worth further investigations.

Animals ; Brain ; pathology ; Brain Ischemia ; etiology ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Infarction, Middle Cerebral Artery ; complications ; Male ; Malondialdehyde ; metabolism ; NG-Nitroarginine Methyl Ester ; pharmacology ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; metabolism ; pathology ; Simvastatin ; pharmacology

Ovarian hyperstimulation syndrome is a serious complication of ovulation induction and has a diverse clinical spectrum from edema to thromboembolism. Antiphospholipid antibody syndrome, one of the well known hypercoagulable states, can be also manifested as an arterial or venous thrombosis and recurrent spontaneous abortion. Sometimes a patient with antiphospholipid antibodies might not notice a miscarriage and seek for assisted reproduction treatment, which harbors a chance of developing ovarian hyperstimulation syndrome. If this happens, the ovarian hyperstimulation syndrome can exacerbate the thrombotic complication of underlying antiphospholipid antibody syndrome, resulting in a catastrophic vascular event. The authors experienced a case of middle cerebral artery infarct, which developed during ovarian hyperstimulation syndrome in a 33-yr-old woman with a previous history of fetal loss. An elevated titer of anticardiolipin antibodies was noticed and persisted thereafter. The authors suggest screening tests for the presence of antiphospholipid antibodies before controlled ovarian hyperstimulation.
Adult ; Antibodies, Anticardiolipin/blood ; Antiphospholipid Syndrome/*complications/pathology ; Female ; Humans ; Iatrogenic Disease ; Infarction, Middle Cerebral Artery/*etiology/pathology ; Magnetic Resonance Angiography ; Ovarian Hyperstimulation Syndrome/*complications/pathology ; Ovulation Induction ; Pregnancy ; *Pregnancy Complications/pathology

OBJECTIVETo study the relationship between carotid atherosclerosis and cerebral infarction (CI).

METHODSBetween November 2008 and March 2009, 147 CI patients (CI group) and 48 patients with non-cerebrovascular diseases (control group) were enrolled from inpatients of Neurology Department of our hospital. The diagnostic criterion of thickened carotid intima was set as 1.0 mm

RESULTSIn the CI group, 36 (24.5%) patients had normal carotid intima, 22 (15.0%) had thickened carotid intima, and 89 (60.5%) had carotid plaque. In the control group, 22 (45.8%) patients had normal carotid intima, 4 (8.3%) had thickened carotid intima, and 22 (45.8%) had carotid plaque. The severity of carotid atherosclerosis in the CI group was higher than that in the control group (P = 0.022). There was significant difference in the constitution of carotid plaque between the two groups (P = 0.001); the CI group mainly had the soft plaque (55/89, 61.8%), whereas the control group mainly had the hard plaque (17/22, 77.3%). The first three common locations of carotid plaque in both groups were carotid bifurcation (CI group: 73.7%; control group: 64.1%), common carotid artery (CI group: 20.4%; control group: 25.6%), and internal carotid artery (CI group: 5.9%; control group: 10.3%). The location of carotid plaque between the two groups was not significantly different (P = 0.438). There was no difference in the carotid inner diameter or resistance index between the two groups (P > 0.05).

CONCLUSIONSCarotid atherosclerosis is to some extent able to reveal the atherosclerotic condition of cerebral arteries and act as an important predictor for the risk of CI. The color Doppler ultrasonography of carotid arteries can provide a convenient way for the prevention and treatment of CI.

Adult ; Aged ; Aged, 80 and over ; Carotid Arteries ; diagnostic imaging ; pathology ; Carotid Artery Diseases ; complications ; epidemiology ; pathology ; Cerebral Infarction ; epidemiology ; etiology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Risk Factors ; Ultrasonography, Doppler, Color

The effect of recombinant microplasmin (micro-plasmin) on acute cerebral infarction was evaluated in rats, and compared with recombinant tissue plasminogen activator (rt-PA). After the model of middle cerebral artery occlusion (MCAO) was established by autologous blood clots, different doses of micro-plasmin (2.5, 5, and 10 mg x kg(-1)) were administered into the thrombus intra-arterial. Twelve hours after administration of micro-plasmin, the neurological deficit score of rats was recorded and the infarct volumes were determined. Bleeding time (BT), fibrin degradation product (FDP) concentration in serum and thrombin time (TT), prothrombin time (PT) and fibrinogen (FIB) concentration in plasma were tested after administration. Intra-arterial administration of micro-plasmin could reduce significantly neurological deficit score and infarct volumes in MCAO rats. FDP concentration increased significantly as compared with model group. There were no significant differences in TT, PT and BT. FIB concentration reduced markedly as compared with model group, but had no significant difference as compared with sham group. The results suggest that micro-plasmin is effective in treatment of rat acute cerebral infarction, and has no significant influence on fibrinolytic system and blood clotting system, indicating that micro-plasmin may be useful for treatment of acute cerebral infarction, and not lead to hemorrhage. Micro-plasmin seems to be distinguished from clinical used rt-PA by its no hemorrhage effect.
Animals ; Bleeding Time ; Brain ; pathology ; Cerebral Hemorrhage ; etiology ; metabolism ; pathology ; Cerebral Infarction ; drug therapy ; pathology ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Fibrinolysin ; pharmacology ; Infarction, Middle Cerebral Artery ; complications ; Male ; Peptide Fragments ; pharmacology ; Prothrombin Time ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology ; Thrombin Time ; Tissue Plasminogen Activator ; pharmacology

This study is to observe the effect of salvianolic acid B (Sal B) on neural cells damage and neurogenesis in sub-granular zone (SGZ) and sub-ventricular zone (SVZ) after brain ischemia-reperfusion (I/R) in rats. A modified middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion was used. The rats were divided into four groups: sham control group, ischemia-reperfusion group, Sal B 1 and 10 mg x kg(-1) groups. Sal B was consecutively administrated once a day by ip injection after MCAO. The neurogenesis in SGZ and SVZ was investigated by BrdU method 7 days after MCAO. The Nissl staining for neurons in the hippocampal CA1 and cerebral cortex was performed 14 days after MCAO. A beam-walking test was used to monitor the motor function recovery. We found that brain ischemia resulted in an increase of BrdU positive cells both in ipsilateral SGZ and SVZ at 7th day after MCAO. Sal B (10 mg x kg(-1)) significantly increased further the number of BrdU positive cells both in SGZ and SVZ (P < 0.01). Ipsilateral hippocampal neuron damage occurred and CA1 almost lost 14 days after MCAO. Sal B (10 mg x kg(-1)) obviously attenuated the neuron damage and increased the number of neuron both in ipsilateral CA1 and cerebral cortex (P < 0.01). We also observed an obvious improvement of motor function recovery when Sal B (10 mg x kg(-1)) administrated. From the results above we concluded that Sal B stimulated neurogenesis process both in SGZ and SVZ after brain ischemia, and also alleviated neural cells loss and improved motor function recovery after brain ischemia in rats.
Animals ; Benzofurans ; isolation & purification ; pharmacology ; Cell Count ; Cerebral Cortex ; pathology ; Cerebral Ventricles ; pathology ; Dentate Gyrus ; pathology ; Hippocampus ; pathology ; Infarction, Middle Cerebral Artery ; complications ; Male ; Motor Activity ; drug effects ; Neurogenesis ; drug effects ; Neurons ; drug effects ; pathology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; pathology ; physiopathology ; Salvia miltiorrhiza ; chemistry

This study is to investigate the effect of gamma-hydroxybutyric acid receptor (GHBR) on focal cerebral ischemia-reperfusion injury in rats and its mechanism. NCS-356 (the agonist of GHBR) and NCS-382 (the antagonist of GHBR) were adopted as the tool medicine. The ripe male Sprague-Dawley rats weighing 240 - 280 g were randomly divided into seven groups: sham operation group (sham), ischemia-reperfusion group (Isc/R), NCS-356 160 microg x kg(-1) group (N1), NCS-356 320 microg x kg(-1) group (N2), NCS-356 640 microg x kg(-1) group (N3), NCS-382 640 microg x kg(-1) + NCS-356 640 microg x kg(-1) group (NCS-382 + N3), and nimodipine (Nim) 600 microg x kg(-1) group. The middle cerebral artery occlusion (MCAO) model referring to Longa's method with modifications was adopted. The effect of GHBR on behavioral consequence of MCAO rats was studied after 2 h of ischemia-reperfusion. After 24 h of ischemia-reperfusion, part of animals were used to measure the cerebral infarction volume by TTC staining; ischemic cortex of another part of animals were used to measure the content of intracellular free calcium by flow cytometry, the tNOS, iNOS activity and the content of NO by spectrophotometric method, the content of cGMP by radioimmunoassay. The neurological function score and infarction volume rate in Isc/R group rats increased significantly than that in sham group; The content of intracellular calcium ([Ca2+]) of cortex neuron and cGMP, the activities of tNOS and iNOS, and the content of NO in Isc/R group were higher than that in sham group obviously (P < 0.01); These consequence we mentioned of N1, N2, N3 and Nim group were lower than that of Isc/R. NCS-382 + N3 group could significantly antagonize the above effect of N3. Thus, NCS-356 has protective effects against ischemia-reperfusion brain injury by activating GHBR. The neuroprotective effect of GHBR is related with decreasing the content of [Ca2+]i, NO, cGMP and tNOS, iNOS activity in MCAO rats.
Animals ; Benzocycloheptenes ; pharmacology ; Calcium ; metabolism ; Cerebral Cortex ; metabolism ; Cerebral Infarction ; pathology ; Cyclic GMP ; metabolism ; Infarction, Middle Cerebral Artery ; complications ; Male ; Neuroprotective Agents ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; agonists ; antagonists & inhibitors ; metabolism ; Reperfusion Injury ; etiology ; metabolism ; pathology

OBJECTIVETo establish a general method of focal cerebral ischemia model in different varieties of mice.

METHODEach group of healthy adult KM and C57BL/6 mice were randomly divided into control group (n = 10) and MCAO group (n = 10). The mice in MCAO group were applied in the preparation of the MCAO model by intraluminal occlusion using monofilament. Twenty-four hours after operation,the neurologic function was evaluated,middle cerebral artery blood flow was monitored and the infarction volume was calculated by TTC staining, to evaluate the reliability of the model.

RESULTIn the MCAO group, the base value of the cerebral blood flow down of KM and C57BL/6 mice respectively was (81.65 ± 4.59)%, (83.68 ± 6.25)%. The neurological deficit score respectively was (2.30 ± 0.82), (2.50 ± 0.80). TTC staining can clearly show the infarction area, and relatively stable, 24 hours of the survival rate of KM and C57BL/6 mice were 100% and 80% respectively.

CONCLUSIONThe key link is the optimization and improvement of monofilament, temperature, anesthesia and so on. The modified intraluminal occlusion of MCAO using monofilament is a kind of reliable and simple method to establish experimental cerebral ischemia model in mice.

Animals ; Blood Flow Velocity ; Brain ; blood supply ; pathology ; physiopathology ; Brain Ischemia ; complications ; physiopathology ; Cerebrovascular Circulation ; Disease Models, Animal ; Infarction, Middle Cerebral Artery ; complications ; physiopathology ; Male ; Mice, Inbred C57BL ; Middle Cerebral Artery ; pathology ; physiopathology ; surgery ; Nervous System Diseases ; etiology ; physiopathology ; Species Specificity

OBJECTIVETo explore the effects of allicin on the changes of hemorheology in focal cerebral ischemia-reperfusion injury in rats.

METHODMiddle cerebral artery occlusion (MCAO) was used to make focal cerebral ischemia-reperfusion model by intravascular nylon filament occlusion. The protective effects of allicin at different doses were evaluated by investigating neurological function score, infarction volume and water content of brain. The changes of blood rheology were detected.

RESULTCompared with model group, allicin (15, 25 mg x kg(-1)) increased the neurological function score and decreased the water content and infarction volume of brain in rats. Allicin (15, 25 mg x kg(-1)) inhibited the increasing of the blood viscosity, high shear rate reduced viscosity, high shear relative reduced viscosity and low shear relative reduced viscosity.

CONCLUSIONAllicin has protective effects on cerebral ischemia-reperfusion injuries. The mechanism may be related to inhibit the increasing of hemorheology.

Animals ; Blood Viscosity ; drug effects ; Garlic ; chemistry ; Infarction, Middle Cerebral Artery ; complications ; Male ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; blood ; etiology ; pathology ; Sulfinic Acids ; isolation & purification ; pharmacology