Cortical spreading depression increases protein synthesis and upregulates basic fibroblast growth factor.
Protective effects of cortical spreading depression (CSD) against ischemic damage have been demonstrated in cortex when elicited at either 24 h or 3 days prior to ischemia. The present study was carried out to investigate possible mechanisms of neuroprotection following CSD. In Sprague-Dawley rats, 5 M KCl, 5 M NaCl, or physiological saline was applied to the cortex for 1 h. Repetitive CSD waves were elicited only in the KCl group. Measurements of cerebral glucose utilization demonstrated a marked reduction in affected cortex and subcortical regions in both the NaCl and the KCl groups, whereas cortical and hippocampal protein synthesis was discretely increased only in the KCl group. Immunohistochemistry of GFAP demonstrated a rapid activation in reactive astrocytes at 3 days in the KCl group whereas only a discrete activation was observed in the NaCl group. Similar changes were observed for basic fibroblast growth factor. Our results suggest that CSD-induced ischemic tolerance is not due to a reduction in energy metabolism but rather is associated with an upregulation of trophic factors and glial cell activation which might provide a mechanism for a long-lasting neuroprotection.
Kawahara
N
N
Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA. kawahara-tky@umin.ac.jp
Ruetzler
C A
CA
Mies
G
G
Klatzo
I
I
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001345:Autoradiography; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D013181:Cortical Spreading Depression / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
D005904:Glial Fibrillary Acidic Protein; D016222:Fibroblast Growth Factor 2; D005947:Glucose