A Neonatal Mouse Spinal Cord Compression Injury Model

Abstract

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life 1 , this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques 1 . Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections 1 .

Neonatal Rats Exhibit a Predominantly Anti-Inflammatory Response following Spinal Cord Injury

“…The normalized locomotor function that was observed in the maturing infant rats in the current study may represent re-organization or possibly enhanced plasticity occurring after the injury and is complementary to the findings reported following a clip compression injury in mice [62, 63]. The predominantly anti-inflammatory response seen in the neonatal rats would provide a more permissive microenvironment for recovery compared to that seen following an adult SCI.…”

Rapid recovery and altered neurochemical dependence of locomotor central pattern generation following lumbar neonatal spinal cord injury

“…; Züchner et al . ). Injuries were targeted either to spinal segments T8–T10 (Th‐SCC) or T13–L2 (Lb‐SCC), with each injury affecting a single segment within the indicated range (Fig.…”

“…; Züchner et al . ). In this model, we have shown that following a single‐segment thoracic compression injury that results in marked diminution of white matter volume, the obliteration of 90% of neurons at the epicentre of the injured segment, a considerable loss of synaptic contacts onto lumbar motoneurons and an initial paralysis of the hindlimbs, a remarkable behavioural recovery ensues that reinstates essentially normal locomotor function.…”

Cellular reactions and compensatory tissue re‐organization during spontaneous recovery after spinal cord injury in neonatal mice

“…Surgery was performed on 1 day postnatal (P1) mice of the ICR strain as previously described (Boulland et al, ; Züchner et al, ). Briefly, the mouse was deeply sedated using 4% isoflurane (Forene, Abbott GmbH & Co. KG) and local anesthesia with Bupivacaine (AstraZeneca).…”

“…Evidence for this in mammals comes from a limited number of studies (Saunders et al, 1995(Saunders et al, , 1998Wang et al, 1998;Wheaton et al, 2011Wheaton et al, , 2013Boulland et al, 2013), including observations in humans (Hadley et al, 1988;Birney and Hanley, 1989;Hamilton and Myles, 1992;Wang et al, 2004). To better understand the difference in pathophysiology and recovery between the injured immature and adult spinal cord, we recently developed a standardized neonatal mouse spinal cord compression injury model (Boulland et al, 2013;Z€ uchner et al, 2016). The model provides an injury situation that permits a remarkable level of behavioral recovery despite extensive and permanent tissue damage.…”