Plasticity in ascending long propriospinal and descending supraspinal pathways in chronic cervical spinal cord injured rats

Abstract

The high clinical relevance of models of incomplete cervical spinal cord injury (SCI) creates a need to address the spontaneous neuroplasticity that underlies changes in functional activity that occur over time after SCI. There is accumulating evidence supporting long projecting propriospinal neurons as suitable targets for therapeutic intervention after SCI, but focus has remained primarily oriented toward study of descending pathways. Long ascending axons from propriospinal neurons at lower thoracic and lumbar levels that form inter-enlargement pathways are involved in forelimb-hindlimb coordination during locomotion and are capable of modulating cervical motor output. We used non-invasive magnetic stimulation to assess how a unilateral cervical (C5) spinal contusion might affect transmission in intact, long ascending propriospinal pathways, and influence spinal cord plasticity. Our results show that transmission is facilitated in this pathway on the ipsilesional side as early as 1 week post-SCI. We also probed for descending magnetic motor evoked potentials (MMEPs) and found them absent or greatly reduced on the ipsilesional side as expected. The frequency-dependent depression (FDD) of the H-reflex recorded from the forelimb triceps brachii was bilaterally decreased although Hmax/Mmax was increased only on the ipsilesional side. Behaviorally, stepping recovered, but there were deficits in forelimb–hindlimb coordination as detected by BBB and CatWalk measures. Importantly, epicenter sparing correlated to the amplitude of the MMEPs and locomotor recovery but it was not significantly associated with the inter-enlargement or segmental H-reflex. In summary, our results indicate that complex plasticity occurs after a C5 hemicontusion injury, leading to differential changes in ascending vs. descending pathways, ipsi- vs. contralesional sides even though the lesion was unilateral as well as cervical vs. lumbar local spinal networks.

Chronic At- and Below-Level Pain after Moderate Unilateral Cervical Spinal Cord Contusion in Rats

“…20,21 Briefly, rats were anesthetized with ketamine (60 mg/kg), xylazine (6 mg/kg), and acepromazine (6 mg/kg) and given antibiotics (ampicillin, subcutaneously,100 mg/kg, daily for 7 days). After partial C5 laminectomy, the spinal column was stabilized in the Infinite Horizon Impact Device (Precision Systems and Instrumentation, Lexington, KY).…”

“…To evaluate hindlimb locomotor performance, the Basso, Beattie, Bresnahan Locomotor Rating Scale (BBB) was used. 24 The BBB is a 22-point semi-quantitative scale that scores hindlimb locomotion after SCI from complete paralysis (0) to normal and coordinated movement (21). Forelimb locomotor performance was assessed using the forelimb locomotor scale (FLS), 25,26 which is an 18-point scale that ranks forelimb locomotion after cervical SCI based on a range of motion, degree of weight support, and paw placement.…”

“…We then determined the proportion of the spared tissue area on the ipsilesional side of the spinal cord to the tissue area on the contralesional (uninjured) spinal cord. 20,21 To further delineate regions within the white matter that are important for relaying nociceptive information to supraspinal centers associated with pain, we used a pie-shaped overlay that had 12 equal wedges as described previously by Côté and colleagues 21 (inset in Fig. 2D).…”

“…2A, 2B). 20,21 Regardless of the presence or absence of allodynia, nearly all grey matter was eliminated, and only a small outer rim of densly stained white matter remained, predominantly in the lateral and ventral funiculi of the ipsilesional spinal cord. There was no evidence of tissue damage in the contralesional spinal cord.…”

The distribution of spinal evoked potentials across dorsal surface in conditions of dorsal roots transection

“…Для рассмотрения специфики распределения потенциалов поперек дорсальной поверхности спин-ного мозга следует вспомнить специфику внутриспи-нального распространения возбуждения нейронов по интраспинальным путям [11]. Так, обнаружено большое количество межсегментарных связей, обес-печивающих проявление соматотопического пред-ставительства кожных дерматомов внутри серого вещества СМ [12], кроме того, существует ряд ко-миссуральных путей, позволяющих возбуждению пе-реходить с "активированной" -на ипсилатеральную сторону мозга и обратно [13].…”