Spinal Interneuron Axons Spontaneously Regenerate after Spinal Cord Injury in the Adult Feline

Abstract

It is well established that long, descending axons of the adult mammalian spinal cord do not regenerate after a spinal cord injury (SCI). These axons do not regenerate because they do not mount an adequate regenerative response and growth is inhibited at the injury site by growth cone collapsing molecules, such as chondroitin sulfate proteoglycans (CSPGs). However, whether axons of axotomized spinal interneurons regenerate through the inhibitory environment of an SCI site remains unknown. Here, we show that cut axons from adult mammalian spinal interneurons can regenerate through an SCI site and form new synaptic connections in vivo. Using morphological and immunohistochemical analyses, we found that after a midsagittal transection of the adult feline spinal cord, axons of propriospinal commissural interneurons can grow across the lesion despite a close proximity of their growth cones to CSPGs. Furthermore, using immunohistochemical and electrophysiological analyses, we found that the regenerated axons conduct action potentials and form functional synaptic connections with motoneurons, thus providing new circuits that cross the transected commissures. Our results show that interneurons of the adult mammalian spinal cord are capable of spontaneous regeneration after injury and suggest that elucidating the mechanisms that allow these axons to regenerate may lead to useful new therapeutic strategies for restoring function after injury to the adult CNS.

Axons with highly branched terminal regions successfully regenerate across spinal midline transections in the adult cat

“…]; supplemental dosages, 5 mg/kg i.v.). The surgical procedures, peripheral nerve stimulation protocols, and postoperative care procedures have previously been described (Fenrich et al, 2007;Fenrich and Rose, 2009). Briefly, the animal's head was placed in a stereotaxic head-holder, the C2 and C3 vertebra were exposed and the dorsal bone covering the C3 segment was removed.…”

“…These blades were mounted on a microdrive attached to the stereotaxic frame. The lesion protocol has previously been described in detail (Fenrich et al, 2007;Fenrich and Rose, 2009). Briefly, the blade was aligned with the spinal midline on the dorsal surface of the spinal cord at the caudal edge of the planned lesion site.…”

“…For instance, Dray et al (2009) found that mouse spinal DRG axons can regenerate through pinprick SCIs. In addition, we recently showed that axons of some axotomized propriospinal commissural interneurons (PCI) can regenerate through SCI sites in the adult cat (Fenrich and Rose, 2009). However, whether there are certain morphological characteristics that distinguish between axons that cross a lesion site and those that fail to cross a lesion site remains unknown.…”

A Neonatal Mouse Spinal Cord Compression Injury Model

“…During the last decade, increasing evidence obtained from different spinal cord injury (SCI) models has shown that spinal networks can reorganize spontaneously to contribute to functional recovery [1][2][3][4][5][6][7][8][9] . Adaptive plasticity has as a consequence become an important topic in SCI research.…”

Dynamic Motor Compensations with Permanent, Focal Loss of Forelimb Force after Cervical Spinal Cord Injury

“…This may explain why human stepping-like movements are easier to induce aftercervical than thoracic SCI, 9 and also the chronic weakness detected in human arm muscles that receive innervation from spinal levels just caudal to the lesion site. 10 The loss and recovery of forelimb motor function has been studied in several models of cervical SCI in rats, 4,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] cats, [28][29][30] and primates. [31][32][33][34][35] All those studies demonstrated some extent of spontaneous motor function recovery, albeit with persisting deficits as a consequence of interruption of descending axonal tracts or segmental neuronal death.…”