Reactive Gliosis Improves Outcome in an Aged Rat Model of Embolic Stroke

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Introduction: Ischemic damage after stroke results in reactive gliosis leading to formation of the glial scar. Controversy exists whether reactive gliosis promotes or impedes recovery after stroke. Thymosin β4 (Tβ4) is a 5K peptide that improves functional outcome after stroke in young rats. In aged rats, however, Tβ4 reduced infarct volume but did not improve functional outcome.

Hypothesis: We hypothesized that Tβ4 treatment would alter the glial scar in our aged rat model of embolic stroke.

Methods: Aged Male Wistar rats (Charles River, 18-21 months, n=15) were subjected to embolic middle cerebral artery occlusion (MCAO). Rats were randomized to receive Tβ4 (12 mg/kg, Regenerx Biopharmaceuticals, Inc.) or control 24 hrs after MCAO and then every 3 days for 4 additional doses. Modified Neurological Severity Score (mNSS) was measured and all rats were sacrificed 56 days after MCAO. Infarct volume was measured and reactive gliosis was analyzed by measuring GFAP immunoreactive cells along the ischemic boundary zone (IBZ). Data are presented as the % in density along the IBZ compared with the contralateral homologous region on the same section. GLIMMIX was used to test the treatment effect in each section. Correlation was calculated between GFAP, infarct volume and mNSS.

Results and Conclusions: GFAP immunoreactivity was significantly inversely correlated with mNSS (p<0.01), suggesting that rats with greater gliosis have better functional improvement. Moreover, increased GFAP immunoreactivity was marginally inversely correlated with a reduction in infarction volume (p=0.067). Tβ4 did not significantly alter reactive gliosis (213 ± 104% vs 145 ± 45 % in control, mean ±std) (p=0.09). Although these data did not show a Tβ4 treatment effect on reactive gliosis, a significant correlation exists on reactive gliosis and improvement on functional outcome, suggesting that the glial scar may improve functional outcome in the aged rat.



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