Plasminogen activator induction facilitates recovery of respiratory function following spinal cord injury

The possibility that plasminogen activator (PA) plays a role in synaptic plasticity was explored in the spinal cord during the crossed phrenic phenomenon (CPP), where respiratory functional plasticity develops following spinal cord injury. Synaptic remodeling on phrenic motor-neurons occurs during the characteristic delay period following spinal cord injury before CPP recovery of respiratory function. The molecular mechanisms underlying this plasticity are not well-defined. During the critical 1-2 h delay period required for this synaptic plasticity following a C2 hemisection in mice, uPA and tPA mRNAs are rapidly induced in C4-5 ventral spinal cord neurons in the ipsilateral phrenic motor nucleus (PMN), as are uPA and tPA protein levels. A role for uPA in CPP spinal cord plasticity is confirmed by the impaired ability of uPA knockout mice to acquire a good CPP response by 6 h post-hemisection and their lack of structural remodeling of PMN synapses that underlies development of the CPP response. (C) 2007 Elsevier Inc. All rights reserved.