The role and therapeutic potential of heat shock proteins in haemorrhagic stroke

Abstract

Heat shock proteins (HSPs) are induced after haemorrhagic stroke, which includes subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH). Most of these proteins function as neuroprotective molecules to protect cerebral neurons from haemorrhagic stroke and as markers to indicate cellular stress or damage. The most widely studied HSPs in SAH are HSP70, haeme oxygenase‐1 (HO‐1), HSP20 and HSP27. The subsequent pathophysiological changes following SAH can be divided into two stages: early brain injury and delayed cerebral ischaemia, both of which determine the outcome for patients. Because the mechanisms of HSPs in SAH are being revealed and experimental models in animals are continually maturing, new agents targeting HSPs with limited side effects have been suggested to provide therapeutic potential. For instance, some pharmaceutical agents can block neuronal apoptosis signals or dilate cerebral vessels by modulating HSPs. HO‐1 and HSP70 are also critical topics for ICH research, which can be attributed to their involvement in pathophysiological mechanisms and therapeutic potential. However, the process of HO‐1 metabolism can be toxic owing to iron overload and the activation of succedent pathways, for example, the Fenton reaction and oxidative damage; the overall effect of HO‐1 in SAH and ICH tends to be protective and harmful, respectively, given the different pathophysiological changes in these two types of haemorrhagic stroke. In the present study, we focus on the current understanding of the role and therapeutic potential of HSPs involved in haemorrhagic stroke. Therefore, HSPs may be potential therapeutic targets, and new agents targeting HSPs are warranted.

Osteopontin as a candidate of therapeutic application for the acute brain injury

“…Inflammation plays a crucial role in the pathogenesis of acute brain injury. 9,16,72,73 Potentially exacerbating secondary brain injury via inflammatory cascade in the acute stage, whereas beneficially promoting tissue remodelling and functional repair, inflammatory response induced by acute brain injury is suggested to be a double-edged sword. 74 By early inhibition of inflammatory cascade, the coordination of pro-inflammatory and anti-inflammatory responses leads to the alleviation of the brain injury and better patient outcome.…”

“…[6][7][8] The latter further consists of subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) and accounts for approximately 10%-20% of strokes yet has higher mortality vs the former. [9][10][11][12][13] TBI refers to sudden damage caused by mechanical force, occurring in traffic accidents, blast, wars, violence, terrorism, falls and sporting activity. 14 TBI is currently the major source of fatality in young adults, with an annual global economic loss of approximately US$ 400 billion.…”

Underlying Mechanisms and Potential Therapeutic Molecular Targets in Blood-Brain Barrier Disruption after Subarachnoid Hemorrhage

“…Heat shock protein 70 (HSP 70), a member of the HSP family of evolutionarily conserved molecular chaperones, can decrease the activity of MMP-9, and then mediate BBB disruption and cell death through aberrant proteolysis. This helps to reduce the inflammation and brain edema that occurs during EBI [ 105 ]. The activation of TLR4 after SAH can activate both NF-κB and MAPKs, and it can also upregulate pro-inflammatory cytokines and mediators, as well as matricellular proteins [ 82 ].…”

Neuroprotective and Angiogenesis Effects of Levetiracetam Following Ischemic Stroke in Rats

“…VEGF is regulated by the transcriptional hypoxia-inducible factor-1 (HIF-1), which regulates gene transcription to facilitate adaptation and survival after hypoxia-ischemia (Hong et al, 2019). Heat shock protein 70 (HSP70) in mice has been shown to provide protection from cerebral ischemia in an animal model of stroke, suggesting that there is a correlation between induction of HSP and resistance to damage (Doeppner et al, 2017;Shao et al, 2019).…”