Search

Objectives: Cerebral ischemia has been proposed as a contributing mechanism to secondary neuronal injury after intracranial hemorrhage (ICH). The search for surrogate parameters that allow treatment stratification for spontaneous ICH continues. We aimed to examine perihemorrhagic ischemic changes with an animal experimental MRI study., Methods: A high field MRI compatible setup for male Wistar rats was established using a double injection model. ICH was stereotactically placed into the right basal ganglia of 29 Wistar rats. Coronal T2-WI, T2*-WI and DWI were generated with a 2.35 T animal MRI scanner 15 min, 60 min and 210 min after ICH. Clot signal characteristics, clot volumes and normalized ADC values were analyzed in four hematoma regions (core, periphery, outer rim, healthy ipsilateral tissue) in all sequences., Results: T2*-WI and DWI reliably demonstrated ICH in 100% with only small deviation from the applied volume (-20% to +26%) whereas T2-WI failed to conspicuously show ICH. There were no perihemorrhagic ADC decreases consistent with ischemic cytotoxic edema but a mild vasogenic edema surrounding the ICH could be observed., Conclusion: T2*-WI and DWI are accurate for the diagnosis of hyperacute ICH. According to serial and crossectional ADC analysis, there is no hint towards the existence of a perihemorrhagic ischemic area that might be saved by early intervention. Future studies should focus on perfusion and metabolic/neurotoxic studies of this particular area and neurotoxic properties of the surrounding edema.

Clinical data clearly show that elevated body temperature contributes to an unfavorable outcome after ischemic and hemorrhagic stroke. Two promising therapeutic strategies arise from this observation: (1) treatment of fever aiming to sustain normothermia and (2) induced hypothermia, targeting core body temperatures below 36.5°C. A limited number of studies investigated antipyretic strategies after acute stroke and their results were rather disappointing in terms of clinical efficacy. For that reason, it remains unproven, whether sufficient fever treatment improves functional outcome. On the other hand, strong experimental evidence supports neuroprotective effects of induced hypothermia after stroke. Yet, clinical data on this topic remain preliminary and rely on a limited number of patients, mostly enrolled in nonrandomized trials. Therefore, induced hypothermia may be considered safe and feasible after ischemic stroke, but little can be said regarding efficacy. This review summarizes the data, both on fever treatment and induced hypothermia following stroke, starting with a synopsis of the most important experimental investigations, leading to the latest clinical trials. Given the promising data and the lack of successful acute neuroprotective therapies available thus far, suggestions are given for future investigation on both topics. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Fever after acute cerebral injury is associated with unfavorable functional outcome and increased mortality, but there is controversy about the optimal antipyretic treatment. This study investigated an institutional standard operating procedure (SOP) for fever treatment in stroke patients including a sequence of pharmacologic and physical interventions. Methods: A 4-step antipyretic SOP was established for patients with acute cerebral ischemia or hemorrhage and a body temperature ≥37.5°C within the first 6 days after admission. Data on the course of body temperature, duration of fever and achievement of normothermia were recorded. Results were compared to a historic control group that underwent conventional treatment. Results: A total of 77 patients (mean age 70.4 ± 14.2 yeas) received 331 antipyretic interventions. Sequential administration of paracetamol (n = 219), metamizole (n = 71) and calf packing (n = 24) resulted in a significant drop in body temperature after 60 min in each instance. In 5 of 9 cases which were refractory to previous attempts, normothermia followed the infusion of ice-cooled saline. In more than 90% of cases treated per protocol, normothermia was achieved within 120 min. Compared to conventional treatment, fever burden was significantly lower within the first 4 days after admission (p < 0.001). Conclusion: This SOP may help to optimize antipyretic treatment for stroke patients. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective: To determine total energy expenditure (TEE) in patients with acute ischemic stroke in the territory of the middle cerebral artery (MCA), treated with moderate hypothermia (33 degrees C).Design and Setting: Prospective study in a neurological ICU.Patients: Ten consecutive patients with severe MCA infarction undergoing moderate hypothermia.Measurements and Results: Indirect calorimetry was performed continuously over the first 6 days after admission. Mean daily TEE decreased significantly from 1549 before initiation of hypothermia to 1099, 1129, and 1157 on the first, second, and third days of hypothermia, respectively and returned to baseline values after hypothermia was terminated. The ratio of TEE to predicted basal energy expenditure declined from 1.01 before induction of hypothermia to an average of 0.74 during steady state of hypothermia and increased to 1.16 after rewarming.Conclusions: We found a significant fall in TEE in sedated, curarized, and ventilated ischemic stroke patients during moderate hypothermia. Indirect calorimetry appears to be a useful tool for measuring energy expenditure in these patients, as predicted basal energy expenditure overestimates the caloric requirements during hypothermia. [ABSTRACT FROM AUTHOR]

We have previously shown that exogenous application of brain-derived neurotrophic factor (BDNF) reduces infarct volume in the cortical ischemic penumbra after experimental focal ischemia [Stroke 31 (2000) 2212–2217]. Since BDNF is known to modulate the expression and function of various neurotransmitter receptors, we addressed the question whether BDNF may act via modification of postischemic ligand binding to excitatory NMDA and AMPA and/or inhibitory GABAA receptors, respectively. Transient focal cerebral ischemia was induced in male Wistar rats for 2 h using the suture occlusion technique. A period of 30 min after occlusion of the middle cerebral artery, BDNF (300 μg/kg per hour in vehicle; n=5) or vehicle alone (n=5) was continuously infused intravenously for 3 h. Using quantitative receptor autoradiography, postischemic ligand binding of [3H]MK-801, [3H]AMPA and [3H]muscimol was analyzed in the ischemic core, the ischemic cortical penumbra and corresponding regions of the contralateral hemisphere. Transient focal ischemia caused a significant reduction of [3H]muscimol binding to GABAA receptors within the ischemic cortical penumbra of placebo-treated rats. This was largely prevented by exogenous application of BDNF. [3H]MK-801 and [3H]AMPA binding values were also reduced in the cortical penumbra and the corresponding area of the contralateral hemisphere. Our data suggest that the neuroprotective effect of BDNF against ischemic damage in the cortical penumbra may be mediated in part by maintained activity of the inhibitory GABAergic system which likely counteracts glutamate induced excitotoxicity. [Copyright &y& Elsevier]

Abstract: We investigated the ability of granulocyte-colony stimulating factor (G-CSF) on inhibiting glutamate release by microdialysis in a rat stroke model. Male Wistar rats (n =15) were treated with either intravenous saline or G-CSF (60μg/kg) 30min after temporary middle cerebral artery occlusion (MCAO). G-CSF significantly attenuated the release of glutamate in the infarcted striatum from 30 minutes to 180 minutes after tMCAO compared with control (p <0.05). Infarct volume in G-CSF treated group (135±13mm3) reduced significantly compared to control (181±10mm3) at 24 hours after tMCAO. The result of present study show that G-CSF possess an ability to inhibit excitotoxicity after ischemic stroke. [Copyright &y& Elsevier]