How to treat stroke in rats? - briefly
Effective management of experimental cerebral ischemia in rodents includes timely intravenous administration of tissue‑plasminogen activator or alternative thrombolytics, combined with neuroprotective agents such as NMDA antagonists, antioxidants, and anti‑inflammatory drugs. Post‑acute care involves controlled hypothermia, physiotherapy, and systematic assessment of neurological recovery using standardized behavioral tests.
How to treat stroke in rats? - in detail
Experimental cerebral ischemia in rodents requires a reproducible protocol that balances lesion severity with animal welfare. The most widely adopted model involves transient occlusion of the middle cerebral artery, which produces a focal infarct comparable to human ischemic stroke.
The occlusion procedure begins with induction of anesthesia using isoflurane (1–2 % in oxygen) or a ketamine‑xylazine cocktail. Core temperature is maintained at 37 °C with a feedback‑controlled heating pad. A midline neck incision exposes the carotid bifurcation; the external carotid artery is ligated, and a silicone-coated filament (0.20–0.30 mm diameter) is advanced through the internal carotid until resistance indicates blockage of the middle cerebral artery. Occlusion time typically ranges from 60 to 120 minutes, after which the filament is withdrawn to permit reperfusion.
Peri‑operative care includes pre‑emptive analgesia (buprenorphine 0.05 mg/kg subcutaneously) and postoperative monitoring of respiratory function, hydration status, and neurological deficits. Immediate administration of tissue‑type plasminogen activator (tPA) can be performed at 10 mg/kg intravenously within 30 minutes of reperfusion for studies examining thrombolytic efficacy; dosage adjustments may be required for specific experimental designs.
Neuroprotective strategies are frequently combined with the occlusion model. Common agents and their typical regimens are:
- NMDA‑receptor antagonists (e.g., MK‑801, 0.1 mg/kg intraperitoneally) administered within 15 minutes of reperfusion.
- Antioxidants (e.g., N‑acetylcysteine, 150 mg/kg intraperitoneally) given immediately after occlusion and repeated every 12 hours for 48 hours.
- Anti‑inflammatory compounds (e.g., minocycline, 45 mg/kg intraperitoneally loading dose, followed by 22.5 mg/kg twice daily).
Post‑acute management focuses on maintaining normoglycemia, providing accessible water and softened chow, and preventing urinary retention with manual bladder expression as needed. Antibiotic prophylaxis (e.g., enrofloxacin 10 mg/kg subcutaneously) is reserved for cases with evident infection.
Rehabilitation protocols enhance functional recovery and reduce secondary degeneration. Standard approaches include:
- Daily forced forelimb use training on a rotating cylinder for 15 minutes.
- Ladder rung walking test three times per week to assess skilled locomotion.
- Enriched environment housing (nesting material, tunnels, running wheels) for continuous sensory stimulation.
Outcome evaluation integrates behavioral, imaging, and histological endpoints. Behavioral batteries comprise the neurological deficit score, adhesive removal test, and Morris water maze for cognitive assessment. Magnetic resonance imaging (T2‑weighted and diffusion‑weighted sequences) performed at 24 hours and 7 days post‑stroke quantifies lesion volume and edema. Histopathology employs cresyl violet staining for infarct delineation and immunohistochemistry for markers such as NeuN (neuronal survival) and Iba1 (microglial activation).
Adhering to this comprehensive regimen ensures reproducible infarct generation, effective acute intervention, and systematic assessment of therapeutic efficacy in rat models of cerebral ischemia.