Left-Right Side-Specific Neuropeptide Mechanism Mediates Contralateral Responses to a Unilateral Brain Injury

Area of Science:

• Neuroscience
• Neurobiology
• Spinal Cord Research

Background:

• Neuropeptides play a role in lateralized brain functions.
• Unilateral brain injury (UBI) leads to sensorimotor deficits on the opposite side of the body.
• The role of opioid neuropeptides in mediating these asymmetric responses post-UBI is not fully understood.

Purpose of the Study:

• To investigate if opioid neuropeptides mediate asymmetric processes induced by UBI.
• To compare the effects of opioid antagonists on hindlimb responses following left-sided and right-sided brain injuries in rats.
• To explore the lateralization of opioid system involvement in sensorimotor deficits post-UBI.

Main Methods:

• Induction of unilateral brain injury (UBI) in rats.
• Assessment of hindlimb postural asymmetry (HL-PA) and withdrawal reflexes (EMG) in response to UBI.
• Administration of general and selective opioid antagonists (naloxone, β-funaltrexamine, nor-binaltorphimine, naltrindole) to evaluate their effects on asymmetries.
• Analysis of opioid gene expression and peptide levels in the lumbar spinal cord.

Main Results:

• UBI induced hindlimb postural asymmetry and altered withdrawal reflexes in the contralesional limb.
• Naloxone affected some asymmetries but did not alter EDL reflex asymmetry.
• Selective antagonists showed injury side-specific effects: μ- and κ-antagonists affected right UBI, while δ-antagonist affected left UBI.
• Lateralized opioid gene expression and impaired coordination with neuroplasticity genes were observed post-UBI.

Conclusions:

• The spinal opioid system can mediate or counteract injury effects, with differential roles depending on injury side.
• Lateralized opioid circuits in the spinal cord differentially control responses to left and right brain injuries.
• These findings highlight a novel mechanism of lateralized control in sensorimotor recovery after brain injury.