Does eicosapentaenoic acid (EPA) inhibit cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage?

Background –  Cerebral vasospasm following subarachnoid hemorrhage (SAH) is a significant cause of morbidity and mortality and recent studies indicate that Rho-kinase plays an important role in the occurrence of such cerebral vasospasm. Eicosapentaenoic acid (EPA), an n -3 polyunsaturated fatty acid, inhibits sphingosylphosphorylcholine (SPC)-induced Rho-kinase activation in vitro , so this study examined whether EPA prevented cerebral vasospasm occurrence after SAH in patients.
Methods –  The trial population was 101 patients with SAH subjected to craniotomy and clip application. EPA was orally administered at a daily dose of 1800 mg EPA from day 4 to day 14 to 73 patients; the other 28 constituted the control group, receiving no EPA.
Results –  EPA significantly curtailed both the occurrence of symptomatic vasospasm (14% EPA group, 36% control, P  = 0.019) and of cerebral infarction because of cerebral vasospasm (4% EPA group, 29% control, P  = 0.001). Moreover, the percentage of patients with a clinically good outcome was significantly higher in the EPA group (85%, P  = 0.022) than in control (64%); there were no deaths in the EPA group but three (11%) in control ( P  = 0.020).
Conclusion –  These findings suggest EPA inhibits symptomatic cerebral vasospasm and cerebral infarction after SAH and also improves clinical prognosis.     

Therapeutic potential of peroxisome proliferator-activated receptor γ agonist rosiglitazone in cerebral vasospasm after a rat experimental subarachnoid hemorrhage model

The pathogenesis of cerebral vasospasm is closely associated with inflammation and immune response in arterial walls. Recently, the authors proved the key role of Toll-like receptor (TLR)4 in the development of vasospasm in experimental subarachnoid hemorrhage (SAH) model. Because peroxisome proliferator-activated receptor (PPAR) gamma agonists are identified as effective inhibitors of TLR4 activation, we investigated the anti-inflammation properties of PPAR-gamma agonist rosiglitazone in basilar arteries in a rat experimental SAH model and evaluated the effects of rosiglitazone on vasospasm. Inflammatory responses in basilar arteries were assessed by immunohistochemical staining for intercellular molecule (ICAM)-1 and myeloperoxidase (MPO). Expression of TLR4 was determined by western blot analysis. The degree of cerebral vasospasm was evaluated by measuring the mean diameter and cross-sectional area of basilar arteries. Rosiglitazone suppressed the SAH-induced inflammatory responses in basilar arteries by inhibiting the TLR4 signalling. Furthermore, rosiglitazone could attenuate cerebral vasospasm following SAH. Therefore, we suggested that PPAR-gamma agonists may be potential therapeutic agents for cerebral vasospasm.     

The rise of soluble platelet-derived growth factor receptor β in CSF early after subarachnoid hemorrhage correlates with cerebral vasospasm

Platelet-derived growth factor β (PDGFβ) has been proposed to contribute to the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH), and soluble PDGFRβ (sPDGFRβ) is considered to be an inhibitor of PDGF signaling. We aimed at determining the sPDGFRβ concentrations in the cerebrospinal fluid (CSF) of patients with aneurysmal SAH (aSAH) and analyzing the relationship between sPDGFRβ level and CVS. CSF was sampled from 32 patients who suffered aSAH and five normal controls. Enzyme-linked immunosorbent assay was performed to determine the sPDGFRβ concentrations in the CSF. Functional outcome was assessed using modified Rankin scale (mRS) at 6 months after aSAH. CVS was identified using transcranial Doppler or angio-CT or DSA. The cutoff of sPDGFRβ for CVS was defined on the ROC curve. The concentrations of sPDGFRβ following aSAH were both higher than those of normal controls on days 1–3 and 4–6, and peaked on days 7–9 post-SAH. The cutoff value of sPDGFRβ level on days 1–3 for CVS was defined as 975.38 pg/ml according to the ROC curve (AUC?=?0.680, p?=?0.082). In addition, CSF sPDGFRβ concentrations correlated with CVS (r?=?0.416, p?=?0.018), and multivariate analysis indicated that sPDGFRβ level higher than 975.38 pg/ml on days 1–3 was an independent predictor of CVS (p?=?0.001, OR?=?19.22, 95% CI: 3.27–113.03), but not for unfavorable outcome after aSAH in the current study. CSF sPDGFRβ level increases after aSAH and is higher in patients who developed CVS, and sPDGFRβ level higher than 975.38 pg/ml on days 1–3 is a potential predictor for CVS after SAH.     

Relationship between brain interstitial fluid tumor necrosis factor-α and cerebral vasospasm after aneurysmal subarachnoid hemorrhage

Tumor necrosis factor-α (TNF-α) has a crucial role in the onset of hemolysis-induced vascular injury and cerebral vasoconstriction. We hypothesized that TNF-α measured from brain interstitial fluid would correlate with the severity of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH). From a consecutive series of 10 aSAH patients who underwent cerebral microdialysis (MD) and evaluation of vasospasm by CT angiogram (CTA) or digital subtraction angiography (DSA), TNF-α levels from MD were measured at 8-hour intervals from aSAH days 4–6 using enzyme-linked immunosorbent assay. An attending neuroradiologist blinded to the study independently evaluated each CTA and DSA and assigned a vasospasm index (VI). Five patients had a VI < 2 and 5 patients had a VI > 2, where the median VI was 2 (range 0–13). The median log TNF-α area under the curve (AUC) was 1.64 pg/mL 1 day (interquartile range 1.48–1.71) for the VI < 2 group, and 2.11 pg/mL 1 day (interquartile range 1.95–2.47) for the VI > 2 group (p < 0.01). Thus, in this small series of poor-grade aSAH patients, the AUC of TNF-α levels from aSAH days 4–6 correlates with the severity of radiographic vasospasm. Further analysis in a larger population is warranted based on our preliminary findings.     

Effect of restraint stress on depression-like behaviors in rats after transient focal cerebral ischemic injury

BACKGROUND: Restraint stress is a typical psychophysiological stressor. Simulating the early passion and difficulty in walking of patients after attack of stroke meets onset features. OBJECTIVE: To evaluate the effect of restraint stress on depression-like behaviors in rats after transient focal cerebral ischemic injury, and to investigate the feasibility for its being as modeling method of depression model after stroke. DESIGN: A randomized controlled animal experiment. SETTING: Department of Clinical Medicine, Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA. MATERIALS: Forty-eight male Sprague-Dawley rats, weighing 240–270 g, provided by the Experimental Animal Center of the Fourth Military Medical University of Chinese PLA were used in the current study. METHODS: The experiments were carried out in the Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA between August 2005 and August 2006. ①Experiment intervention: The rats were randomized into middle cerebral artery occlusion-reperfusion (MCAO) +stress group, simple MCAO group, sham-operation + stress group and simple sham-operation group, with 12 rats in each group. Rats in the first two groups were developed into cerebral ischemia/reperfusion models by suture-occluded method. Rats in the MCAO+stress group were modeled and restraint stress scheme was performed. At week 5 after modeling, the rats were placed in self-made restraining tubes, 2 hours/time, once a day, for 2 successive weeks. The common carotid artery, external and internal carotid arteries of rats in the latter two groups were exposed. The stress way of sham-operation+ stress group was the same as that of MCAO+ stress group. ②The neurological status grading and motor performance evaluation (screen test, rota-rod test and balance beam test) were conducted in rats with simple sham-operation group and MCAO group before, 1st and 28th days after modeling. Depression-like behavior test was performed in the rats of each group by sucrose preference test and open field test at the end of the experiment. MAIN OUTCOME MEASURES: Changes of depression-like behaviors of rats in each group. RESULTS: Forty-eight rats were involved in the experiment. Two rats with meningeal irritation sign were excluded from simple MCAO group, and one rat in the MCAO+stress group died of some unclear causes during the experiments. The other 45 rats entered the stage of finial analysis. ① Depression-like behavior assessment results: The rats in the MCAO+ stress group had a significantly decreased preference for sucrose solution, crossing and rearing scores, and increased immobility duration after the 14-day restraint stress, compared with those in other three groups (all P < 0.05). ②The neurological status grading and motor performance evaluation: There were significant differences in the two indexes of rats in the simple MCAO group before, 1st and 28th days after modeling (P < 0.01), while there was no significant difference before and 28th days after modeling (P > 0.05). There were no significant changes in sham-operation group at each time point (P > 0.05). CONCLUSION: After being exerted restraint stress, the rats with transient focal ischemic injury may show obvious depression-like behaviors. Therefore, restraint stress can be used as a novel animal modeling method for further studying biological mechanism in central nervous system of post-stroke depression animals.     

Effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats

BACKGROUND: It has been shown that although brain does not contain lining endothelial lymphatic vessel, it has lymphatic drain. Anterior lymphatic system of lymphatic vessel in brain tissue plays a key role in introducing brain interstitial fluid to lymphatic system; however, the significance of lymphatic drain and the effect on cerebral edema remains unclear. OBJECTIVE: To investigate the effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats. DESIGN: Randomized controlled animal study. SETTING: Institute of Cerebral Microcirculation of Taishan Medical College and Department of Neurology of Affiliated Hospital. MATERIALS: A total of 63 healthy adult male Wistar rats weighing 300-350 g were selected in this study. Forty-seven rats were used for the morphological observation induced by lymphatic drain and randomly divided into three groups: general observation group (n =12), light microscopic observation group (n =21) and electronic microscopic observation group (n =14). The rats in each group were divided into cerebral lymphatic block subgroup and sham-operation control subgroup. Sixteen rats were used for observing the effect of cerebral lymphatic block on cortical evoked potential, in which the animals were randomly divided into sham-operation group (n =6) and cerebral lymphatic block group (n =10). METHODS: The experiment was carried out in the Institute of Cerebral Microcirculation of Taishan Medical College from January to August 2003. Rats in cerebral lymphatic block group were anesthetized and separated bilateral superficial and deep cervical lymph nodes under sterile condition. Superior and inferior boarders of lymph nodes were ligated the inputting and outputting channels, respectively, and then lymph node was removed so as to establish cerebral lymphatic drain disorder models. Rats in sham-operation control group were not ligated the lymphatic vessel and removed lymph nodes, and other operations were as the same as those in cerebral lymphatic block group. Morphological changes of the brain and alterations of latency of cortical evoked potential were detected on the 1st, 2nd, 3rd, 5th, 7th, 10th and 15th days after operation under general, light microscope and electronic microscope observations. MAIN OUTCOME MEASURES: ① Cerebral morphological changes; ② latent changes of cortical evoked potential. RESULTS: A total of 63 rats were involved in the final analysis. ① Cerebral morphological changes: General observation showed that, for cerebral lymphatic block rats, the surface of brain was pale and full, and cerebral gyrus was wide and flattened sulci after cerebral lymphatic block; and cerebral tissue space prolongation, increased interstitial fluid, neuronal degeneration and necrosis, diffused phagocytes and satellitosis were observed under light microscope. Neuronal swell and necrosis, glial cell swell, apparent subcellular changes such as mitochondron were observed under electronic microscope. ② Latent changes of cortical evoked potential: As compared with sham-operation control group, latency of cortical evoked potential in cerebral lymphatic blockage group prolonged on the 5th day and 7th day after cerebral lymphatic block [(6.28±0.23), (6.97±0.35) ms; (6.23±0.22), (7.12±0.20) ms; P < 0.01]. CONCLUSION: ① Cerebral lymphatic block plays an important role in cerebral morphology, and may result in abnormality of sensitive impulse conduction and prolong latency of cortical evoked potential. ② Examination of cortical evoked potential is easy and convenient, so it is regarded as a key index for lymphatic disturbed cerebral injury.     

Effect ofβ-adrenoceptor agonists on apomorphine-induced turning in rats

Summary The-adrenoceptor agonists clenbuterol, salbutamol and formoterol were found to inhibit apomorphine-induced turning behavior in rats with unilateral nigrostriatal lesions. The inhibitory effect of clenbuterol was antagonized by (–)-propranolol, but unaffected by practolol (which does not cross the blood-brain barrier), indicating a central localization of the-adrenoceptors mediating the inhibitory effect. A dopamine-releasing activity of clenbuterol did not seem to be responsible for the effect, because known dopamine-releasing agents (amphetamine, methylphenidate) did not antagonize apomorphine-induced turning behavior. Furthermore-methyl-p-tyrosine pretreatment did not prevent the inhibitory effect of clenbuterol. Since L-5-hydroxytryptophan did not mimic the inhibitory effect of clenbuterol, it was concluded that the inhibition of turning behavior ist not mediated by the interaction of clenbuterol with the serotonin system. The finding that clenbuterol depressed locomotor activity in the same dose range as it inhibited apomorphine-induced turning tentatively suggests that clenbuterol inhibits apomorphine-induced turning behavior by its central-adrenoceptor mediated sedative action.     

Effect of tetramethylpyrazine on the spatial learning and memory function of rats after focal cerebral ischemia

BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arterial resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE: To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN: A randomized controlled trial. SETTING: Department of Human Anatomy and Histological Embryology, School of Medicine, Xi'an Jiaotong University. MATERIALS: Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi'an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd (Lot Number: 2004051106, Specification: 2 mL/piece). METHODS: The experiments were carried out in School of Medicine of Xi'an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method: sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. MAIN OUTCOME MEASURES: The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. RESULTS: Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [(23.92±2.21), (41.84±3.74), (39.50±3.80), (31.38±3.72), (61.60±3.61) s, P < 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [(36.27±3.42) %, (35.84±2.54)%, (38.43±3.08)%, (36.51±1.96)%, (22.24±3.46)%; (11±1), (10±1), (8±1), (8±1), (4±1) times, P < 0.01]. ② In the morphological observation, the numbers of neurons in ipsilateral (left) parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [(98±8), (65±5), (53±6), (57±6), (37±6)/0.625 mm2, P < 0.01], but the number of neurons in left hippocampus had no obvious differences among the groups (P > 0.05). CONCLUSION: TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.     

The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model

This study investigated the effects of 18β-glycyrrhetinic acid (GA) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. All subjects (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) I/R, (3) GA, and (4) GA+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with the vehicle for 10 days. In the GA group, mice were given GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the GA+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with the same dose of GA for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidaitons and a decrease in elements of the antioxidant defense systems. However, GA treatment was protective against the oxidative effects of I/R by inducing significant increases in antioxidant defense systems and a significant decrease of lipid peroxidations. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by GA treatment. Therefore, the current study demonstrated that GA treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, GA may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, it may be a viable and safe alternative treatment for ischemic stroke in humans.     

Effect of electroacupuncture on synaptic transmission in dentate gyrus of the hippocampus in cerebral ischemic injured rats

IN T R O D U C T IO N Long-term potentiation (LTP ) is an essentialphenom enon concern- ing cerebral plasticity. It w as routinely used as a basic cellular m odel for the study of m em ory. LTP could be induced by m ul- ti-factors constructing the externa…     

Identification of blood-brain barrier function following subarachnoid hemorrhage in rats at different stages*☆

BACKGROUND： Recent studies have indicated that blood-brain barrier （BBB） disruption following subarachnoid hemorrhage （SAH） significantly correlates with the development of brain injury and poor prognosis of patients subjected to SAH. OBJECTIVE： To investigate both functional and structural changes related to BBB in various phases after SAH in rats through quantitative and qualitative methods. DESIGN, TIME AND SETTING： This experiment, a completely randomized design and controlled experiment, was performed at the Department of Neurosurgery, the Second Affiliated Hospital of Chongqing University of Medical Sciences from June 2006 to March 2007. MATERIALS： A total of 128 female, healthy, Sprague-Dawley rats were selected for this study. Main reagents and instruments： Evans Blue dye （Sigma Company, USA）, fluorescence spectrophotometer （Shimadzu Company, Japan）, and transmission electron microscope （Olympus Company, Japan）. METHODS： The included 128 rats were randomly divided into two groups： sham-operated group （n = 16） and SAH group （n = 112）. Rats in the SAH group were divided into seven subgroups： 6, 12, 24, 36, 48, 60, and 72 hours after SAH （16 rats for each time point）. Experimental SAH was induced by blood injection into the pre-chiasmatic cistern （300 μ L）. The sham-operated group received an equivalent volume of normal saline solution （300 μ L） injected into the subarachnoid space. MAIN OUTCOME MEASURES： Brain tissue water content was determined by the wet-dry method. BBB permeability in the cerebral cortex was determined by Evans Blue dye and fluorescent spectrophotometer. The ultrastructural changes in BBB were observed with transmission electron microscope. RESULTS： Compared with the sham-operated group, SAH induced a significant increase in brain water content between 24 and 60 hours （F = 888.32, P 〈 0.05）. Brain water content increased to a maximum by 36 hours after SAH, normalizing by 72 hours. Evans Blue content in the cerebral corte     

The ferric iron chelator 2,2′-dipyridyl attenuates basilar artery vasospasm and improves neurological function after subarachnoid hemorrhage in rabbits

We investigated the efficacy of the ferrous iron (Fe²⁺) chelator 2,2′-dipyridyl (DP) to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH). Thirty-six New Zealand white rabbits were randomly assigned to four groups: untreated control, SAH, SAH + dimethyl sulfoxide (DMSO) vehicle, and SAH + DP. SAH was induced by injection of autologous blood into the cisterna magna and then DP or vehicle was infused into the cistern magna for 5 days (20 mg/kg/day or an equal volume of DMSO). Neurological deficit score (NDS) was used to assess neurological function and cerebral angiography to measure basilar artery (BA) diameter following SAH. TUNEL staining was used to detect BA endothelial cell apoptosis, and immunohistochemistry and Western blotting to assess changes in caspase-3 protein levels 5 days post-SAH. The SAH + DP group had a significantly larger mean BA diameter and lower mean NDS post-SAH compared to the SAH + DMSO and SAH groups (p < 0.05). TUNEL-positive cell numbers and caspase-3 levels were significantly reduced in BA endothelial cells of the SAH + DP group as compared to the SAH and SAH + DMSO groups (p < 0.05). The iron chelator DP reduced vasospasm and neurological sequelae in rabbits, likely by chelating the Fe²⁺ in oxyhemoglobin and reducing oxidative stress-induced endothelial cell apoptosis.     

Imaging of hypoxic�Cischemic penumbra with 18F-fluoromisonidazole PET/CT and measurement of related cerebral metabolism in aneurysmal subarachnoid hemorrhage

This study aimed to characterize hypoxic, but salvageable, tissue imaged by ¹⁸F-fluoromisonidazole (¹⁸F-FMISO), combining with perfusion-computed tomography (PCT) for regional cerebral blood flow (rCBF) measurement and metabolism by microdialysis (MD) in aneurysmal subarachnoidal hemorrhage (SAH) patients. ¹⁸F-FMISO positron-emission tomography (PET)/CT was performed within the period of possible vasospasm (day 6.8±3 after SAH) in seven SAH patients. In parallel, rCBF was determined within the MD region of interest (MD-ROI) (n=5). The MD catheter was inserted into the brain parenchyma with highest risk for ischemia; extracellular levels of glutamate and energy metabolites were registered at time of PET and hourly for 10 days. Twelve-month outcome was evaluated. In asymptomatic patients (n=3) no hypoxia was detected and glutamate levels were low (<10 mmol/L), whereas symptomatic patients had higher glutamate concentrations (P<0.001). Increased ¹⁸F-FMISO uptake within the MD-ROI (n=3) was related to higher glutamate levels, while rCBF was above the ischemic range. Hypoxia (increased ¹⁸F-FMISO uptake) was present in symptomatic patients and associated with relevant metabolic derangement of extracellular glutamate levels, whereas energy metabolism and rCBF were preserved. This technique has the potential to improve our understanding of the role of cellular hypoxia in aneurysmal SAH.     

Effects of N^G-nitro-L-arginine on focal cerebral ischemic injury in rats

IN T R O D U C T IO N Throm bolysis is the m ajor therapeutic m eans clinically for acute stroke. But som etim es som e patients’cerebral injury m ay be ag- gravated after throm bolysis. It has been becom ing a new subject to research and produce effecti…     

Effect of topiramate on partial excitatory amino acids in hippocampal dentate gyrus of rats after alcohol withdrawal

IN T R O D U C T IO NA lcohol is a com m on addictive substance, and long-term ethanol drinking m ay lead to alcoholdependence. O nce the drinking am ount of alcohol is reduced or w ithdraw n suddenly, specific w ithdraw al sym ptom s w illoccur, such as …     

Mild hypothermia effects on matrix metalloproteinase-9 expression in the perihematomal region of rats following experimental intracerebral hemorrhage**☆

BACKGROUND： Matrix metalloproteinase-9 （MMP-9） expression increases with intracerebral hemorrhage, and participates in the pathophysiological processes of secondary brain injury after intracerebral hemorrhage.
OBJECTIVE： To investigate the effects of mild hypothermia on MMP-9 expression and brain edema in the perihematomal region of experimental intracerebral hemorrhage rats.
DESIGN, TIME AND SETTING： The randomized, controlled experiment was performed at the Central Laboratory of Shandong Provincial Hospital between May and September 2007.
MATERIALS： Seventy-two, Wistar, male rats, 12-weeks old, were used for this study. Rabbit anti-MMP-9 primary antibody was purchased from Boster, China.
METHODS： Wistar rats were equally and randomly divided into normothermia and mild hypothermia groups. The two groups each comprised control, 6-hour intracerebral hemorrhage, 24-hour intracerebral hemorrhage, 48-hour intracerebral hemorrhage, 72-hour intracerebral hemorrhage, and l-week intracerebral hemorrhage subgroups, with six rats in each subgroup. Rat models of intracerebral hemorrhage were established by injecting 100 μL of autologous blood into the rat caudate nucleus. Rats in the mild hypothermia group received four hours of local mild hypothermia immediately following the injection. lntracerebral temperature was maintained at （33 ± 0.5） ℃. Subsequently, intracerebral temperature was spontaneously recovered at 25 ℃. Rats in the control subgroup were not injected with autologous blood and received only with intracerebral hemorrhage.
MAIN OUTCOME MEASURES： Brain water content and MMP-9 expression surrounding the hematoma region. RESULTS： MMP-9 expression increased at 6 hours, and brain edema reached a peak at 48 hours after intracerebral hemorrhage. MMP-9 expression was significantly decreased in the mild hypothermia group compared with the normothermia group at each time point （P 〈 0.05）.
CONCLUSION： Mild hypothermia can significantly inhibit MMP-9 overexpression and reliev     

Effect of interferon-α on DOI-induced wet-dog shakes in rats

Summary Acute (1h) intraperitoneal (ip) treatment with interferon (IFN)--2a (300IU/g) significantly inhibited wet-dog shakes (WDS) induced by (±)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI; 0.5, 1.0mg/kg), which is mediated by serotonin (5-hydroxytryptamine; 5-HT)₂ receptor in rats. IFN- did not affect spontaneous locomotion. The inhibition of DOI (0.5mg/kg)-induced WDS by IFN- was dose (90–300 IU/g)- and time (1–6 h)-dependent, and was prevented by 30 min pretreatment with naltrexone (NLTX; 1.0mg/kg, ip), an opioid receptor antagonist. Acute (1h) intracerebroventricular (icv) treatment with IFN- (1,500IU/rat) also inhibited DOI (0.5mg/kg)-induced WDS, and the effect was blocked by NLTX (50g/rat, icv). These results suggest that IFN- may modulate 5-HT₂ receptor-mediated behavior through opioid receptors in the central nervous system.Abbreviations CNS central nervous system - DOI (±)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane - 5-HT 5-hydroxytryptamine (serotonin) - icv intracerebroventricular - IFN interferon - ip intraperitoneal - IU international unit - NLTX naltrexone - sc subcutaneous - WDS wet-dog shakes