Therapeutic Hypothermia in Ischemic Stroke Management

Therapeutic hypothermia (TH) has emerged as a promising intervention in the acute management of ischaemic stroke by tempering the cascade of deleterious biochemical and inflammatory processes triggered by focal cerebral occlusion. By lowering cerebral temperature to the mild-moderate range (32–35 °C), metabolic demand is reduced, excitotoxic neurotransmitter release is curtailed, free radical formation is limited and blood–brain barrier integrity is better preserved. Advances in endovascular cooling devices, selective regional perfusion techniques and pharmacologically induced hypothermia have enhanced precise control of target temperature while minimising systemic side effects. Preclinical models consistently demonstrate that early induction and optimal duration of TH shrink infarct size, conserve white matter structure and improve functional recovery. Clinical translation has focused on integrating TH with thrombolysis or mechanical thrombectomy, refining timing protocols and managing shivering and coagulopathy to ensure safety and efficacy. Collectively, these developments underscore the global significance of temperature modulation as a neuroprotective strategy in ischaemic stroke care.

Research from Nature Portfolio

Recent experimental studies have elucidated combination strategies to potentiate the neuroprotective actions of mild hypothermia. In one rodent model of middle cerebral artery occlusion, mild cooling (33–35 °C) was combined with phenothiazine neuroleptics, resulting in accelerated temperature reduction, amplified activation of the PI3K/Akt anti-apoptotic pathway, decreased infarct volumes and improved neurological scores. In primary cortical neuron cultures subjected to oxygen–glucose deprivation, co-treatment with mild hypothermia and selected neuroprotective agents stabilised mitochondrial membrane potential, diminished intracellular calcium accumulation and reduced reactive oxygen species, highlighting synergistic mechanisms by which targeted temperature management can enhance cellular resilience during ischaemic insult.

Therapeutic Hypothermia in Ischemic Stroke Management publication trend

The graph below shows the total number of articles in therapeutic hypothermia in ischemic stroke management across all publications each year (not limited to Nature Index journals).

Technical terms

Therapeutic hypothermia: Controlled reduction of core or regional brain temperature to attenuate ischaemia-induced damage.

Ischaemic cascade: Sequential cellular and molecular events—such as excitotoxicity, oxidative stress and inflammation—initiated by oxygen and glucose deprivation.

Reperfusion injury: Paradoxical exacerbation of tissue damage upon restoration of blood flow, mediated by free radicals and inflammatory mediators.

Neuroprotection: Strategies or interventions aimed at preserving neuronal structure and function during or after cerebral ischaemia.

Middle cerebral artery occlusion (MCAO): Experimental or clinical interruption of the middle cerebral artery flow to model focal ischaemic stroke.

Infarct volume: Quantitative measure of permanently damaged brain tissue following an ischaemic event.

References

1. Hypothermic neuroprotection by targeted cold autologous blood transfusion in a non-human primate stroke model. Science Bulletin (2023).
2. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. BMC Cardiovascular Disorders (2010).
3. Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury. Scientific Reports (2014).
4. Endovascular Cooling Catheter for Selective Brain Hypothermia: An Animal Feasibility Study of Cooling Performance. American Journal of Neuroradiology (2015).
5. Phenothiazines Enhance Mild Hypothermia-induced Neuroprotection via PI3K/Akt Regulation in Experimental Stroke. Scientific Reports (2017).
6. Intravenous thrombolysis in combination with mild hypothermia therapy in the treatment of acute cerebral infarction. Pakistan Journal of Medical Sciences (2019).