How does a stroke occur in rats? - briefly
In laboratory rodents, ischemic stroke is typically produced by inserting a filament through the carotid artery to block the middle cerebral artery, creating localized cerebral blood flow reduction. Alternative methods include intracerebral injection of vasoconstrictors such as endothelin‑1 to achieve targeted vessel constriction.
How does a stroke occur in rats? - in detail
Stroke induction in laboratory rats relies on reproducible vascular manipulations that mimic human cerebrovascular injury. Two principal categories exist: ischemic models, which restrict arterial blood supply, and hemorrhagic models, which cause intracerebral bleeding.
In ischemic protocols, the most widely employed technique blocks the middle cerebral artery (MCA). The intraluminal filament method inserts a silicone-coated nylon suture through the external carotid artery, advancing it until the MCA origin is occluded. Researchers can maintain occlusion for a defined period (typically 30–120 minutes) before withdrawing the filament to allow reperfusion. This approach produces a core of irreversible infarction surrounded by a penumbra of salvageable tissue, closely resembling human focal ischemia. Alternative methods include:
- Embolic clot delivery: a pre‑formed autologous clot is injected into the internal carotid artery, producing a distal occlusion that models thromboembolic stroke.
- Photothrombotic occlusion: systemic injection of a photosensitizer followed by focused illumination creates a localized thrombus, allowing precise lesion size control.
- Endothelin‑1 microinjection: a potent vasoconstrictor is deposited near the MCA, inducing transient vasospasm and ischemia without mechanical injury.
Hemorrhagic models generate intracerebral hemorrhage by disrupting vascular integrity. Two common techniques are:
- Collagenase injection: stereotaxic infusion of bacterial collagenase into the striatum degrades basal lamina, leading to spontaneous bleeding and hematoma expansion.
- Autologous blood infusion: a defined volume of the animal’s own blood is injected into brain parenchyma, reproducing the mass effect and secondary injury seen in human intracerebral hemorrhage.
The pathological cascade following arterial obstruction begins with abrupt reduction in cerebral blood flow, causing depletion of adenosine triphosphate and loss of ion homeostasis. Neuronal depolarization triggers massive glutamate release, overstimulating NMDA receptors and allowing calcium influx. Elevated intracellular calcium activates proteases, lipases, and nitric‑oxide synthase, generating free radicals and lipid peroxidation. Concurrently, endothelial dysfunction promotes blood‑brain barrier breakdown, facilitating vasogenic edema. Inflammatory cells infiltrate the ischemic zone, releasing cytokines and matrix metalloproteinases that exacerbate tissue damage. Cell death occurs through necrosis in the infarct core and apoptosis in the surrounding penumbra. In hemorrhagic scenarios, the expanding hematoma produces mechanical compression, while blood degradation products (e.g., hemoglobin, iron) provoke oxidative stress and inflammatory responses similar to those in ischemia.
Standard outcome measures include neurological scoring, infarct volume quantification via TTC staining or MRI, and histopathological assessment of neuronal loss, gliosis, and microglial activation. These models provide a controlled platform for evaluating neuroprotective agents, reperfusion strategies, and surgical interventions aimed at mitigating cerebrovascular injury.