How can a stroke be treated in a rat? - briefly
Acute reperfusion in rodents is achieved with tissue‑type plasminogen activator administration or mechanical clot extraction, after which neuroprotective measures such as therapeutic hypothermia, pharmacologic agents, and stem‑cell transplantation are employed to enhance recovery. Complementary supportive care—including fluid balance, analgesia, and physiotherapy—rounds out the treatment protocol.
How can a stroke be treated in a rat? - in detail
Experimental stroke in laboratory rodents is typically induced by middle‑cerebral‑artery occlusion (MCAO) using either intraluminal filament or photothrombotic techniques. Treatment protocols focus on three phases: acute reperfusion, neuroprotection, and post‑ischemic rehabilitation.
Acute reperfusion strategies employ recombinant tissue‑plasminogen activator (rt‑PA) administered intravenously within 3–4 hours after occlusion. Effective dosing in rats ranges from 5 to 10 mg/kg, delivered as a bolus followed by an infusion. Alternative thrombolytics such as urokinase or tenecteplase are used at comparable weight‑adjusted doses. Mechanical thrombectomy models, wherein a micro‑snare extracts the filament, provide a platform for evaluating endovascular devices.
Neuroprotective interventions target excitotoxicity, oxidative stress, inflammation, and apoptosis. Common agents include:
- NMDA‑receptor antagonists (e.g., MK‑801, 0.3 mg/kg i.p.).
- Free‑radical scavengers (e.g., N‑acetylcysteine, 150 mg/kg i.p.).
- Anti‑inflammatory compounds (e.g., minocycline, 45 mg/kg i.p.).
- Mitochondrial stabilizers (e.g., cyclosporine A, 10 mg/kg i.p.).
These drugs are typically given within the first hour post‑ischemia and repeated at 12‑ and 24‑hour intervals to sustain therapeutic levels.
Cell‑based therapies provide regenerative support. Intravenous infusion of mesenchymal stem cells (1 × 10⁶ cells in 0.5 ml saline) at 24 hours after insult promotes angiogenesis and neuronal survival. Direct intracerebral transplantation of neural progenitor cells (2 × 10⁵ cells) into the peri‑infarct zone yields similar benefits but requires stereotaxic surgery.
Hypothermia reduces metabolic demand and limits infarct expansion. Whole‑body cooling to 33 °C for 3 hours, initiated within 30 minutes of occlusion, attenuates lesion size by 30–40 % in most reports. Surface cooling pads or chilled intraperitoneal saline are practical methods for maintaining target temperature.
Rehabilitation begins after the acute phase and incorporates forced‐use paradigms, treadmill training, and skilled reaching tasks. Daily sessions of 30 minutes for 2–3 weeks improve forelimb function and enhance cortical plasticity, as measured by intracortical microstimulation mapping.
Outcome assessment combines imaging, histology, and behavioral testing. Magnetic resonance diffusion‑weighted imaging performed 24 hours post‑stroke quantifies lesion volume. Cresyl violet staining of coronal sections provides infarct area and edema correction. Behavioral batteries—Neurological Deficit Score, Rotarod latency, and adhesive removal test—offer quantitative functional readouts.
In summary, effective management of experimental cerebral ischemia in rodents integrates timely thrombolysis, targeted neuroprotective agents, cell‑based regeneration, controlled hypothermia, and structured rehabilitation, each validated by reproducible physiological and functional endpoints.