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Neuroprotection in ischemic stroke--combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia.
Brain Res. 2004 Oct 15; 1023(2):272-8.BR

Abstract

We have recently demonstrated marked neuroprotective efficacy of a combination therapy with magnesium (calcium- and glutamate-antagonist), tirilazad (antioxidant) and mild hypothermia (MTH) in a rat model of transient focal cerebral ischemia. In the present study, we investigated MTH under conditions of permanent focal cerebral ischemia. In part I, 20 Sprague-Dawley rats were subjected to 6 h of permanent, laser-Doppler flowmetry (LDF) controlled middle cerebral artery occlusion (MCAO). Drugs were administered 30 min before and 1 h after MCAO. Hypothermia (33 degrees C) was maintained for 2 h. Infarct size was planimetrically determined after 6 h. In part II, 29 rats were assigned to the same treatment arms and subjected to 7 days of permanent MCAO. Neurological deficits and body weight were assessed daily. Infarct size was determined on day 7. In part I, MTH significantly reduced infarct formation by 52% after 6 h. In part II, high mortality within the first 3 days was observed in both groups. Treated animals showed a significantly better postoperative weight gain on day 7 and neurological recovery on days 6 and 7 compared to controls without significant differences in infarct volume. MTH seems to exert its neuroprotective properties even in a setting of permanent cerebral ischemia. High mortality and absence of infarct reduction after 7 days might be due to model limitations. Neurological recovery, the most important clinical outcome parameter, is significantly improved in 7-day survivors. Significant neuroprotection under conditions of permanent ischemia and former promising results in transient ischemia justify further investigations of MTH.

Authors+Show Affiliations

Department of Neurosurgery, Ludwig-Maximilians-Universität, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany. kschoell@nc.med.uni-muenchen.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15374753

Citation

Schöller, Karsten, et al. "Neuroprotection in Ischemic Stroke--combination Drug Therapy and Mild Hypothermia in a Rat Model of Permanent Focal Cerebral Ischemia." Brain Research, vol. 1023, no. 2, 2004, pp. 272-8.
Schöller K, Zausinger S, Baethmann A, et al. Neuroprotection in ischemic stroke--combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia. Brain Res. 2004;1023(2):272-8.
Schöller, K., Zausinger, S., Baethmann, A., & Schmid-Elsaesser, R. (2004). Neuroprotection in ischemic stroke--combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia. Brain Research, 1023(2), 272-8.
Schöller K, et al. Neuroprotection in Ischemic Stroke--combination Drug Therapy and Mild Hypothermia in a Rat Model of Permanent Focal Cerebral Ischemia. Brain Res. 2004 Oct 15;1023(2):272-8. PubMed PMID: 15374753.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotection in ischemic stroke--combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia. AU - Schöller,Karsten, AU - Zausinger,Stefan, AU - Baethmann,Alexander, AU - Schmid-Elsaesser,Robert, PY - 2004/01/05/accepted PY - 2004/9/18/pubmed PY - 2005/1/26/medline PY - 2004/9/18/entrez SP - 272 EP - 8 JF - Brain research JO - Brain Res. VL - 1023 IS - 2 N2 - We have recently demonstrated marked neuroprotective efficacy of a combination therapy with magnesium (calcium- and glutamate-antagonist), tirilazad (antioxidant) and mild hypothermia (MTH) in a rat model of transient focal cerebral ischemia. In the present study, we investigated MTH under conditions of permanent focal cerebral ischemia. In part I, 20 Sprague-Dawley rats were subjected to 6 h of permanent, laser-Doppler flowmetry (LDF) controlled middle cerebral artery occlusion (MCAO). Drugs were administered 30 min before and 1 h after MCAO. Hypothermia (33 degrees C) was maintained for 2 h. Infarct size was planimetrically determined after 6 h. In part II, 29 rats were assigned to the same treatment arms and subjected to 7 days of permanent MCAO. Neurological deficits and body weight were assessed daily. Infarct size was determined on day 7. In part I, MTH significantly reduced infarct formation by 52% after 6 h. In part II, high mortality within the first 3 days was observed in both groups. Treated animals showed a significantly better postoperative weight gain on day 7 and neurological recovery on days 6 and 7 compared to controls without significant differences in infarct volume. MTH seems to exert its neuroprotective properties even in a setting of permanent cerebral ischemia. High mortality and absence of infarct reduction after 7 days might be due to model limitations. Neurological recovery, the most important clinical outcome parameter, is significantly improved in 7-day survivors. Significant neuroprotection under conditions of permanent ischemia and former promising results in transient ischemia justify further investigations of MTH. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/15374753/Neuroprotection_in_ischemic_stroke__combination_drug_therapy_and_mild_hypothermia_in_a_rat_model_of_permanent_focal_cerebral_ischemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(04)01200-4 DB - PRIME DP - Unbound Medicine ER -