10/20 Stroke Flashcards
• What are strokes
o Strokes are also known as focal cerebral ischemia. Ischemic stroke results from transient or permanent reduction in blood flow to a restricted territory of a major brain artery. Caused by an ambolus or thrombosis. Hemorrhagic stroke is breakage of blood vessel.
• Types of stroke
o Ischaemic stroke: when artery feeding brain is blocked by clot or fat. Most common, less likely to be fatal.
o Haemorrhagic stroke: blood vessel burst. Less common, more fatal. Uncontrolled hypertension. Only treatment is surgery
o Transient ischaemic attack: mini-stroke. Interrupted blood flow only briefly. Warning.
• Common areas affected by stroke
o Frontal lobe (personality, behavior,decisions). Contralateral movement affects
o Parietal: speech and sensation
o Occipital—vision
o Cerebellum—balance, coordination
o Brain stem—vital functions. Rare to have a stroke here but most life threatening
o Temporal lobe—hearing and speech. Long term memory.
• Experimental methods for inducing stroke
o Global ischemia—2 or 4 vessel occlusion, circulatory arrest.
o Focal ischemia—craniectomy (transient with surgical clip or permanent with cauterization), no craniectomy (transient MCAO/reperfusion, thromboembolic/lysis, endothelin 1. Or permanent, only first step, non-clot embolic.)
o Most models include Middle cerebral artery.
o For these, distal or proximal electrocoagulation can be used. Intraparenchymal endothelin-1 microinjection, or intraluminal injection of thrombin and topical application of endothelin-1
• Experimental models of stroke
o Thromboembolic: similar to human, non invasive. Large variability
o In situ-thromboembolic: similar to human, non-invasive. Craniotomy
o Non-clot microsphere: multifocal lesion. High variability, permanent
o Intraluminal monofilament: reproducible infacts, temp or perm, non-invasive. High mortality rates
o Direct surgical: exact, reproducible, high survival. Craniotomy
o Photothromotic: well defined, no craniotomy. Early lesion development is different
o Endothelin-1: application to different brain regions. Limited control of intensity and duration.
• The ischemic cascade
o Core and penumbra of ischemia are induced by focal blockade of cerebral arteries. In the core there is ionic failure, depolarization, and decreased glucose use. Cells die very quickly without glucose.
o Early events (minutes): accumulation of extracellular NTs mostly glutamate which leads to excitotoxicity due to swelled astrocytes.
o Excitotoxic cascade: NMDA activation increases Ca which leads to decrease in ATP and energy failure as well as increase NO, ONOO- and activation of PARP-1 and cell death. NMDA blockage reduces infarct size.
o ionic dysregulation: decrease of ATp impaires ability to remove Na and Ca. this causes oxidative stress and cell death. K efflux plays a role in apoptotic cascade and contributes to ROS production and ATP depletion.
o Hours to days—apoptosis and neuroinflammation. Free radicals and early BBB injury. Increased cytokine, chemokine, and microglial activation to try to heal.
o Late events (neuroinflammation, blood-brain barrier disruption, vasogenic edema)
• Neuroprotective strategies in Stroke
o Targeting penumbra to salvage tissue. Reperfusion therapy (thrombolytics, mechanical clot removal). Best is combination neuroprotective agents with recanalization.
