Although mild therapeutic hypothermia is an effective neuroprotective strategy for cardiac arrest/resuscitated patients, and asphyxic newborns, recent randomized controlled trials (RCTs) have equally shown good neurological outcome between targeted temperature management at 33 °C versus 36 °C, and have not shown consistent benefits in patients with traumatic brain injury (TBI). We aimed to determine the effect of therapeutic hypothermia, while avoiding some limitations of earlier studies, which included patient selection based on Glasgow coma scale (GCS), delayed initiation of cooling, short duration of cooling, inter-center variation in patient care, and relatively rapid rewarming. We conducted a multicenter RCT in patients with severe TBI (GCS 4-8). Patients were randomly assigned (2:1 allocation ratio) to either therapeutic hypothermia (32-34 °C, n = 98) or fever control (35.5-37 °C, n = 50). Patients with therapeutic hypothermia were cooled as soon as possible for ≥ 72 h and rewarmed at a rate of <1 °C/day. All patients received tight hemodynamic monitoring under intensive neurological care. The Glasgow Outcome Scale was assessed at 6 months by physicians who were blinded to the treatment allocation. The overall rates of poor neurological outcomes were 53% and 48% in the therapeutic hypothermia and fever control groups, respectively. There were no significant differences in the likelihood of poor neurological outcome (relative risk [RR] 1.24, 95% confidence interval [CI] 0.62-2.48, p = 0.597) or mortality (RR 1.82, 95% CI 0.82-4.03, p = 0.180) between the two groups. We concluded that tight hemodynamic management and slow rewarming, together with prolonged therapeutic hypothermia (32-34 °C) for severe TBI, did not improve the neurological outcomes or risk of mortality compared with strict temperature control (35.5-37 °C).

Background and Purpose-Our previous studies have demonstrated that oxidative DNA injury occurs in the brain after intracerebral hemorrhage (ICH). We therefore examined whether edaravone, a free-radical scavenger, could reduce ICH-induced brain injury. Methods-These experiments used pentobarbital-anesthetized, male Sprague-Dawley rats that received an infusion of either 100 L autologous whole blood (ICH), FeCl 2 , or thrombin into the right basal ganglia. The rats were humanely killed 24 hours later. There were 4 sets of experiments. In the first, the dose-dependent effects of edaravone on ICH-induced brain injury were examined by measuring brain edema and neurologic deficits. In the second set, apurinic/apyrimidinic abasic sites and 8-hydroxyl-2Ј-deoxyguanosine, which are hallmarks of DNA oxidation, were investigated after treatment for ICH. In the third, the effect of delayed treatment with edaravone on ICH-induced injury was determined, whereas the fourth examined the effects of edaravone on iron-and thrombin-induced brain injury. Results-Systemic administration of edaravone immediately or 2 hours after ICH reduced brain water content 24 hours after ICH compared with vehicle (PϽ0.05). Edaravone treatment immediately or 2 hours after ICH also ameliorated neurologic deficits (PϽ0.05). Edaravone also attenuated ICH-induced changes in apurinic/apyrimidinic abasic sites and 8-hydroxyl-2Ј-deoxyguanosine and reduced iron-and thrombin-induced brain injury. Conclusions-Edaravone attenuates ICH-induced brain edema, neurologic deficits, and oxidative injury. It also reduces iron-and thrombin-induced brain injury. These results suggest that edaravone is a potential therapeutic agent for ICH.

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Background and Purpose-Intraischemic mild hypothermia has been shown to be neuroprotective in reducing cerebral infarction in transient focal ischemia. As a more clinical relevant issue, we investigated the effect of delayed intraischemic and postischemic hypothermia on cerebral infarction in a rat model of reversible focal ischemia. We also examined the effect of hypothermia on the inflammatory response after ischemia-reperfusion to assess the neuroprotective mechanism of brain hypothermia. Methods-Rats were subjected to 2 hours of middle cerebral artery occlusion followed by 22 hours of reperfusion under the following protocols: (1) rats were treated with normothermia (37.0°C, 4 hours) and then housed in room temperature (25°C, 18 hours) and (2) rats were treated with hypothermia (33.0°C, 4 hours, brain temperature modulation was started 30 minutes before the reperfusion) and then housed in cold temperature (5°C, 18 hours). Animals were killed 24 hours after the onset of ischemia. The infarct volume was examined with 2,3,5-triphenyl-tetrazolium chloride staining. The accumulation of polymorphonuclear leukocytes (PMNLs) and the expression of intercellular adhesion molecule-1 mRNA were evaluated in both groups. Results-A significant reduction (PϽ0.05) in infarct volume was found in the hypothermia group compared with the normothermia group. Compared with the normothermia group, hypothermic treatment also significantly reduced the accumulation of PMNLs (PϽ0.01) and inhibited the overexpression of intercellular adhesion molecule-1 mRNA at 22 hours of reperfusion after 2 hours of ischemia. Conclusions-Ischemic brain damage can be reduced with delayed intraischemic and prolonged postischemic hypothermia in a focal model of transient cerebral ischemia in rats. The neuroprotective mechanism of hypothermia may be mediated by suppression of PMNL-mediated inflammatory response after ischemia-reperfusion in this model. Key Words: cerebral ischemia, focal Ⅲ hypothermia Ⅲ intercellular adhesion molecule-1 Ⅲ neutrophils Ⅲ peroxidase I schemic stroke is a leading source of disability in elderly persons, and much emphasis in research is being placed on the early treatment of stroke. The advancement of intravascular techniques and thrombolytic agents, especially recombinant tissue plasminogen activator (rtPA), has been shown to reduce functional deficits within an optimal time window. 1,2 The acceleration of recanalization with thrombolytic agents can salvage brain tissue in an ischemic area from irreversible cell death. However, the time window for effective treatment is narrow because longer durations of ischemia and subsequent reperfusion increase the likelihood of brain edema formation and hemorrhagic transformation. 3 This phenomenon has been demonstrated in various tissues, especially in the heart and lung, and been termed "reperfusion injury." The understanding and treatment of reperfusion injury are important in the new era of reperfusion therapy for cerebral stroke. See Editorial Comment, page 1989There has been renewe...

Our study indicated that MMP-2 and MMP-9 expressions are prognostic factors predicting the recurrence of meningioma, independent of proliferative potential.

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The neurotoxicity of epsilon-toxin, one of the major lethal toxins produced by Clostridium perfringens type B, was studied by histological examination of the rat brain. When the toxin was injected intravenously at a lethal dose (100 ng/kg), neuronal damage was observed in many areas of the brain. Injection of the toxin at a sublethal dose (50 ng/kg) caused neuronal damage predominantly in the hippocampus: pyramidal cells in the hippocampus showed marked shrinkage and karyopyknosis, or so-called dark cells. The dark cells lost the immunoreactivity to microtubule-associated protein-2, a postsynaptic somal and dendric marker, while acetylcholinesterase-positive fibers were not affected. Timm’s zinc staining revealed that zinc ions were depleted in the mossy layers of the CA3 subfield containing glutamate as a synaptic transmitter. The cerebral blood flow in the hippocampus was not altered significantly before or after administration of the toxin, as measured by laser-Doppler flowmetry, excluding the possibility that the observed histological change was due to a secondary effect of ischemia in the hippocampus. Prior injection of either a glutamate release inhibitor or a glutamate receptor antagonist protected the hippocampus from the neuronal damage caused by epsilon-toxin. These results suggest that epsilon-toxin acts on the glutamatergic system and evokes excessive release of glutamate, leading to neuronal damage.