Accelerated glial reactivity to stroke in aged rats correlates with reduced functional recovery.
Following cerebral ischemia, perilesional astrocytes and activated microglia form a glial scar that hinders the genesis of new axons and blood vessels in the infarcted region. Since glial reactivity is chronically augmented in the normal aging brain, the authors hypothesized that postischemic gliosis would be temporally abnormal in aged rats compared to young rats. Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague Dawley rats. The functional outcome was assessed in neurobehavioral tests at 3, 7, 14, and 28 days after surgery. Brain tissue was immunostained for microglia, astrocytes, oligodendrocytes, and endothelial cells. Behaviorally, aged rats were more severely impaired by stroke and showed diminished functional recovery compared with young rats. Histologically, a gradual activation of both microglia and astrocytes that peaked by days 14 to 28 with the formation of a glial scar was observed in young rats, whereas aged rats showed an accelerated astrocytic and microglial reaction that peaked during the first week after stroke. Oligodendrocytes were strongly activated at early stages of infarct development in all rats, but this activation persisted in aged rats. Therefore, the development of the glial scar was abnormally accelerated in aged rats and coincided with the stagnation of recovery in these animals. These results suggest that a temporally anomalous gliotic reaction to cerebral ischemia in aged rats leads to the premature formation of scar tissue that impedes functional recovery after stroke.
Badan
I
I
Department of Neurology, dagger Institute of Psychology, section sign Institute of Pharmacology, Ernst-Moritz-Arndt University of Greifswald, Germany.
Buchhold
B
B
Hamm
A
A
Gratz
M
M
Walker
L C
LC
Platt
D
D
Kessler
Ch
Ch
Popa-Wagner
A
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery; D008264:Macrophages / Q000502:physiology; D008297:Male; D009457:Neuroglia / Q000502:physiology*; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*
D015415:Biomarkers; D011508:Chondroitin Sulfate Proteoglycans; D005904:Glial Fibrillary Acidic Protein