How do rats die from a stroke? - briefly
An experimentally induced cerebral ischemia triggers massive neuronal loss, brain swelling, and disruption of autonomic centers, which quickly leads to respiratory failure. The ensuing edema and systemic collapse cause the animal to die.
How do rats die from a stroke? - in detail
Experimental strokes in rats are usually produced by middle‑cerebral‑artery occlusion (MCAO), photothrombosis, or intracerebral hemorrhage injection. The induced lesion triggers a cascade that culminates in mortality through several overlapping mechanisms.
Energy depletion occurs within seconds of arterial blockage. Loss of ATP impairs ion pumps, causing depolarization, massive glutamate release, and calcium influx. The resulting excitotoxicity damages neuronal membranes and activates proteases that degrade structural proteins. Cytotoxic edema follows, raising intracranial pressure (ICP) and compressing brainstem nuclei that regulate respiration and cardiovascular function.
Vasogenic edema develops as the blood‑brain barrier breaks down. Fluid accumulation in the subarachnoid space further elevates ICP. When ICP surpasses cerebral perfusion pressure, global cerebral blood flow collapses, leading to brain‑stem ischemia and loss of autonomic control.
Hemorrhagic transformation of the infarct can occur spontaneously or after reperfusion. Blood extravasation introduces hemoglobin breakdown products that generate free radicals, aggravating oxidative stress and inflammation. Intracerebral hemorrhage expands the lesion, increases mass effect, and accelerates brain‑stem compression.
Systemic complications contribute to fatal outcomes. Autonomic dysregulation produces cardiac arrhythmias and myocardial depression. Respiratory centers in the medulla become depressed, causing apnea or irregular breathing patterns. Severe metabolic acidosis and hyperkalemia develop as damaged tissue releases intracellular ions, further compromising cardiac function.
The time course of death varies. Immediate mortality (within minutes) is rare and usually linked to massive hemorrhage or abrupt brain‑stem herniation. Most deaths occur within the first 24 hours, driven by rapid edema, rising ICP, and cardio‑respiratory failure. Secondary deaths can arise days later from infection, sepsis, or prolonged metabolic imbalance.
Typical causes of mortality in rodent stroke models include:
- Uncontrolled intracranial pressure leading to brain‑stem herniation
- Cardiac arrhythmias secondary to autonomic collapse
- Respiratory arrest from medullary dysfunction
- Hemorrhagic conversion causing mass effect
- Systemic metabolic derangements (acidosis, hyperkalemia)
Understanding these pathways allows refinement of experimental protocols, such as controlled reperfusion, neuroprotective drug administration, and supportive care, to reduce early mortality and improve the relevance of rodent stroke studies.