By inhibiting pyroptosis to reduce neuroinflammation, PEG-bHb may prevent the development of secondary injury after traumatic brain injury

  • Exp Neurol. 2025 Aug 27:115447. doi: 10.1016/j.expneurol.2025.115447.
Qiang Zeng  1 ,  Guoxing You  1 ,  Weidan Li  1 ,  Jianlei An  2 ,  Zhiyong Huang  2 ,  Xiaoyong Zhang  1 ,  Hong Zhou  1 ,  Yao Xiao  3 ,  Ying Wang  4 ,  Lian Zhao  5
Affiliations
  • 1. Academy of Military Medical Sciences, 100850 Beijing, China.
  • 2. Academy of Military Medical Sciences, 100850 Beijing, China; Department of Critical Care Neurosurgery, China Medical University Aviation General Hospital, 100012 Beijing, China.
  • 3. Academy of Military Medical Sciences, 100850 Beijing, China. Electronic address: [email protected].
  • 4. Academy of Military Medical Sciences, 100850 Beijing, China. Electronic address: [email protected].
  • 5. Academy of Military Medical Sciences, 100850 Beijing, China. Electronic address: [email protected].
PMID: 40882799 DOI: 10.1016/j.expneurol.2025.115447
Abstract

Changes in severe pathological microenvironment of traumatic brain injury (TBI) have important implications for neurological repair, including oxidative stress and intense neuroinflammatory responses. Pyroptosis, a regulated cellular demise process characterized by membrane permeabilization, constitutes a primary contributor to post-traumatic brain injury induced neural inflammatory responses. Regulating the Pyroptosis pathway may alleviate secondary brain injury. Polyethylene glycol-conjugated bovine Hemoglobin (PEG-bHb) is a type of hemoglobin-based oxygen carriers (HBOCs) and is designed for oxygen delivery in transfusion therapy. PEG-bHb exhibits the capacity to bind and release oxygen, promoting oxygen supply in hypoxic tissues. In vivo studies have found that PEG-bHb can elevate regional oxygen saturation after TBI in prehospital stage, effectively inhibit Pyroptosis, attenuate neuroinflammation and oxidative stress, and effectively attenuate the development of secondary brain injury. Furthermore, PEG-bHb has been demonstrated to protect the blood-brain barrier (BBB) by reducing the permeability of BBB and attenuating brain edema. PEG-bHb has been shown to enhance motor, learning, and memory abilities following TBI. Thus, PEG-bHb can act as a promising candidate for TBI treatment.

Keywords
Hemoglobin-based oxygen carries; Mitochondrial dysfunction; Neuroinflammation; Oxidative stress; Pyroptosis; Traumatic brain injury.
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