From the Guidelines
Excitotoxicity is the primary cellular event linked to the exacerbation of ischemic stroke pathophysiology. During an ischemic stroke, blood flow to brain tissue is interrupted, causing energy depletion in neurons. This energy failure leads to excessive release of glutamate, the brain's main excitatory neurotransmitter. The abnormal accumulation of glutamate overstimulates NMDA and AMPA receptors, triggering massive calcium influx into neurons. This calcium overload activates destructive enzymes like proteases, lipases, and endonucleases that damage cellular structures and initiate cell death pathways. Additionally, the calcium influx generates harmful reactive oxygen species and triggers inflammatory responses, further expanding the area of tissue damage beyond the initial ischemic core.
The provided evidence supports this claim, as it discusses the role of mitochondria in ischemic stroke and the involvement of various cellular processes, including excitotoxicity, in the pathogenesis of the disease 1. The evidence highlights the importance of understanding the underlying mechanisms of ischemic stroke to develop effective therapeutic regimens.
Some key points to consider include:
- The role of glutamate in excitotoxicity and its impact on neuronal death 1
- The involvement of mitochondrial dynamics and mitophagy in the regulation of cell survival and death 1
- The generation of reactive oxygen species and the triggering of inflammatory responses in the ischemic brain 1
- The potential for therapeutic interventions targeting excitotoxicity and mitochondrial function to limit neuronal death in ischemic stroke 1
Overall, the evidence suggests that excitotoxicity is a critical component of the pathophysiology of ischemic stroke, and targeting this process may be a promising approach for the development of new therapeutic strategies.
From the Research
Cellular Events Linked to Ischemic Stroke Pathophysiology
The pathophysiology of ischemic stroke is complex and involves various cellular events. The correct answer can be identified by analyzing the given options and the provided evidence.
Analysis of Options
- Option A: Decreased calcium influx and enhanced mitochondrial function. This option is not supported by the evidence, as ischemic stroke is typically associated with increased calcium influx and mitochondrial dysfunction 2.
- Option B: Reduced ATP depletion results in a decrease in intracellular sodium levels. This option is also not supported, as ATP depletion is a hallmark of ischemic stroke, leading to increased intracellular sodium levels 2.
- Option C: Glutamate inhibition and acidosis mitigation. While glutamate inhibition and acidosis mitigation may be beneficial in the context of ischemic stroke, this option does not directly describe a cellular event linked to the exacerbation of ischemic stroke pathophysiology 2.
- Option D: Upregulation of the CCR5 chemokine receptor hampers the recovery. This option is supported by the evidence, as the upregulation of CCR5 has been shown to contribute to the pathogenesis of ischemic stroke, and its inhibition may be neuroprotective 3.
Key Findings
- Ischemic stroke is characterized by a complex series of pathophysiological events, including excitotoxicity, oxidative and nitrative stress, inflammation, and apoptosis 2, 4.
- Chemokines and their receptors, such as CCR5, play a role in the migration of leukocytes and contribute to the pathogenesis of ischemic stroke 3, 5.
- The inhibition of inflammatory cell accumulation in the brain at the early stage of stroke may lead to amelioration of ischemic neurodegeneration 5.
Relevant Evidence
- A study published in 2017 found that knockdown of CCR5 is protective against cerebral ischemia and reperfusion injury, suggesting that CCR5 plays a role in the pathogenesis of ischemic stroke 3.
- Another study published in 2013 found that chemokines are upregulated in the ischemic brain and may be a potential target for future therapies reducing inflammatory cell migration to the brain in early stroke 5.