Neuroserpin: A Potential Neuroprotective Agent in Mild Neonatal Hypoxic-Ischaemic Encephalopathy

Area of Science:

• Neuroscience
• Developmental Biology
• Biochemistry

Background:

• Neonatal hypoxic-ischaemic encephalopathy (HIE) is a major cause of infant death and disability.
• Therapeutic hypothermia is the sole approved treatment for HIE.
• The role of neuroserpin in neonatal brain development and its neuroprotective capacity in HIE remain underexplored.

Purpose of the Study:

• To map the cortical expression of neuroserpin during postnatal development.
• To assess the neuroprotective effects of neuroserpin in a hypoxia-ischaemia (HI) mouse model.
• To investigate the potential of exogenous neuroserpin as a therapeutic agent for neonatal HIE.

Main Methods:

• Utilized neuroserpin knockout (KO) and wild-type (WT) mice in a modified Rice-Vannucci model of HI.
• Administered exogenous neuroserpin to evaluate its effects on HI-induced brain damage.
• Analyzed neuroserpin expression patterns in the developing cortex (postnatal days 4-14).
• Assessed markers of oxidative stress, microglial activation, and astrogliosis.

Main Results:

• Neuroserpin expression peaked in specific cortical layers (5, 6b, 2/3) between postnatal days 8-10.
• Exogenous neuroserpin administration mitigated HI-induced oxidative stress, microglial activation, and reactive astrogliosis in mild HIE.
• Neuroserpin treatment reduced cortical thinning and preserved neuronal distribution.
• No significant difference in overall ischemic brain damage was observed between KO and WT mice, suggesting endogenous neuroserpin is insufficient alone.

Conclusions:

• Endogenous neuroserpin is insufficient for neuroprotection against hypoxia-ischaemia induced brain damage.
• Exogenous neuroserpin demonstrates significant neuroprotective potential in mild neonatal HIE.
• Neuroserpin presents a promising pharmacological target for treating mild neonatal HIE.