Research reportImpact of estrogen receptor beta activation on functional recovery after experimental stroke

- The ERβ ligand AC-131 improves functional recovery after photothrombosis.
- Improvement of recovery by AC-131 was dose dependent.
- The treatment did not affect infarct size.
- Treatment was independent from acute neuroprotective actions by ER.

Acute treatment with 17β-estradiol provides effective neuroprotection during the first days after acute brain injury, however, effects of chronic activation of estrogen receptor beta (ERβ) on recovery of function after experimental stroke have not been investigated. The present study, therefore, was conducted to test if delayed treatment with the specific ERβ ligand 4-(1-phenyl-cyclohexyl)-phenol (AC-131) improves recovery of lost neurological function after permanent focal stroke induced by photothrombosis in adult Sprague-Dawley rats. Treatment was initiated on day 2 after photothrombosis and AC-131 (1, 10, and 50 mg/kg) was administered by daily subcutaneous injections for 14 days. On day 2, 4, 6, 8, 11, 14, and 17 after photothrombosis, functional deficits were assessed by the paw placement test, a standardized grip strength test and an adhesive removal test. Daily treatment with AC-131 significantly improved test scores in all three behavioral tests. Importantly, improved function was not associated with a decrease in infarct volume on day 17 after stroke onset. Our results suggest that increased activity of the ERβ is involved in mechanisms of stroke recovery.