Hypothermia and brain-derived neurotrophic factor reduce glutamate synergistically in acute stroke

• Published in: Experimental neurology 2004-02, Vol.185 (2), p.305-312
• Main Authors: Berger, Christian, Schabitz, Wolf-R., Wolf, Margit, Mueller, Harald, Sommer, Clemens, Schwab, Stefan
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - pharmacology; Brain-Derived Neurotrophic Factor - therapeutic use; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Down-Regulation - physiology; Extracellular-regulated kinase; Glutamate; Glutamic Acid - metabolism; Hypothermia; Hypothermia, Induced - methods; Immunohistochemistry; Injections, Intravenous; Ischemic stroke; Male; Medical sciences; Microdialysis; Neurology; Rats; Rats, Wistar; Stroke - drug therapy; Stroke - metabolism; Stroke - therapy; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2003.10.008

Moderate hypothermia and application of brain-derived neurotrophic factor (BDNF) have separately been identified as neuroprotective strategies in experimental cerebral ischemia. To assess their separate and combined effects on striatal glutamate release in the hyperacute phase of stroke, we inserted microdialysis probes into the striatum of rats 2 h before permanent middle cerebral artery occlusion (MCAO). The animals ( N = 28) were randomly assigned to one of four treatment strategies commencing 30 min after MCAO: (1) hypothermia at 33°C ( n = 7); (2) intravenous BDNF infusion [300 μg/(kg/h) for 2 h, n = 7]; (3) combination of hypothermia and BDNF ( n = 7); (4) control group (saline, n = 7). Infarct size at 5 h after MCAO was assessed with the silver-staining method. Total infarct volume was significantly reduced in the hypothermia (202.7 ± 3.5 mm 3, P = 0.0002) and BDNF group (206.5 ± 6.9 mm 3, P = 0.0006) as compared to control group (254.4 ± 9.3 mm 3). In the combination group, infarct size was further reduced with overall significance in post hoc tests (157.3 ± 6.2 mm 3, P < 0.0001). Postischemic glutamate concentrations in the control group constantly remained significantly higher than in all other treatment groups. At 255 and 270 min after MCAO, striatal glutamate in the combination group decreased significantly more than in animals treated with hypothermia or BDNF alone. Combining hypothermia and BDNF therapy in the acute stage of ischemia has a synergistic effect in attenuating striatal glutamate release and reducing early infarct size.