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Updated: May 29, 2026
A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models
Christa Thoene-Reineke1, Kay Rumschüssel, Kristin Schmerbach
1Center for Cardiovascular Research/Institute of Pharmacology, Charité-Universitätsmedizin Berlin, Berlin, Germany. christa.thoene-reineke@charite.de
Objectives:
The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats.
Methods:
Prevention study: Stroke-prone spontaneously hypertensive rats (SHR-SP) were subjected to high salt and randomly assigned to 4 groups: (1) untreated (NaCl, n = 24), (2) telmisartan (T; n = 27), (3) ramipril (R; n = 27) and (4) telmisartan + ramipril (T+R; n = 26). Drug doses were selected to keep blood pressure (BP) at 150 mmHg in all groups. Neurological signs and stroke incidence at 50% mortality of untreated SHR-SP were investigated. Intervention study: Normotensive Wistar rats were treated s.c. 5 days prior to middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Groups (n = 10 each): (1) sham, (2) vehicle (V; 0.9% NaCl), (3) T (0.5 mg/kg once daily), (4) R (0.01 mg/kg twice daily), (5) R (0.1 mg/kg twice daily) or (6) T (0.5 mg/kg once daily) plus R (0.01 mg/kg twice daily). Twenty-four and 48 h after MCAO, neurological outcome (NO) was determined. Forty-eight h after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and neurotrophin receptor (TrkB) were analysed.
Results:
Stroke incidence was reduced, survival was prolonged and neurological outcome was improved in all treated SHR-SP with no differences between treated groups. In the acute intervention study, T and T+R, but not R alone, improved NO, reduced infarct volume, inflammation (TNFα), and induced TrkB receptor and neuronal survival in comparison to V.
Conclusions:
T, R or T+R had similar beneficial effects on stroke incidence and NO in hypertensive rats, confirming BP reduction as determinant factor in stroke prevention. In contrast, T and T+R provided superior neuroprotection in comparison to R alone in normotensive rats with induced cerebral ischemia.
Insights
Telmisartan and ramipril equally prevented strokes in hypertensive rats by lowering blood pressure. However, telmisartan, alone or combined with ramipril, offered superior neuroprotection against cerebral ischemia in normotensive rats.
Area of Science:
- Cardiovascular Pharmacology
- Neuroscience
- Stroke Research
Background:
- Hypertension significantly increases stroke risk.
- Cerebral ischemia, a common cause of stroke, requires effective neuroprotective strategies.
- Angiotensin II receptor blockers (ARBs) and ACE inhibitors are key antihypertensive agents.
Purpose of the Study:
- To compare the efficacy of telmisartan (an ARB) and ramipril (an ACE inhibitor) in stroke prevention in hypertensive rats.
- To evaluate the neuroprotective effects of telmisartan and ramipril in an acute cerebral ischemia model in normotensive rats.
- To investigate the combined effects of telmisartan and ramipril on stroke and neuroprotection.
Main Methods:
- Stroke-prone spontaneously hypertensive rats (SHR-SP) were treated with telmisartan, ramipril, or both to assess stroke incidence and survival.
- Normotensive Wistar rats underwent middle cerebral artery occlusion (MCAO) to induce ischemia, followed by treatment with telmisartan, ramipril, or combination therapy.
- Neurological outcome, infarct volume, inflammation markers, and neurotrophin receptor TrkB expression were analyzed post-MCAO.
Main Results:
- Telmisartan, ramipril, and their combination similarly reduced stroke incidence and improved neurological outcomes in hypertensive rats.
- In normotensive rats with induced ischemia, telmisartan and the combination therapy significantly improved neurological outcomes and reduced infarct size.
- Telmisartan-containing regimens reduced inflammation (TNFα) and increased TrkB receptor expression and neuronal survival compared to vehicle or ramipril alone.
Conclusions:
- Blood pressure reduction is the primary mechanism for stroke prevention by telmisartan and ramipril in hypertensive rats.
- Telmisartan demonstrates superior neuroprotective effects in acute cerebral ischemia compared to ramipril alone.
- Combination therapy with telmisartan and ramipril offers enhanced neuroprotection in ischemic stroke models.