Protecting motor networks during perinatal ischemia: the case for delta-opioid receptors

Abstract

Perinatal ischemia is a common clinical problem with few successful therapies to prevent neuronal damage. Delta opioid receptor (DOR) activation is a versatile, evolutionarily conserved, endogenous neuroprotective mechanism that blocks several steps in the deleterious cascade of neurological events during ischemia. DOR activation prior to ischemia or severe hypoxia is neuroprotective in spinal motor networks, as well as cortical, cerebellar, and hippocampal neural networks. In addition to providing acute and long-lasting neuroprotection against ischemia, DOR activation appears to provide neuroprotection when given before, during, or following the onset of ischemia. Finally, DORs can be upregulated by several physiological and experimental perturbations. Potential adverse side effects affecting motor control, such as respiratory depression and seizures, are not well established in young mammals and may be mitigated by altering drug choice and method of drug administration. The unique features of DOR-dependent neuroprotection make it an attractive potential therapy that may be given to at-risk pregnant mothers shortly before delivery to provide long-lasting neuroprotection against unpredictable perinatal ischemic events.

Figure 1

Ischemia or severe hypoxia reduces ATP production and initiates a series of deleterious cascade of events that lead to neuronal damage or death. Experimental evidence shows that DOR activation has to the capacity to attenuate or block several steps in the cascade.** Indicates a step that disrupted by DOR activation.