A Long-Term Pilot Study on Sex and Spinal Cord Injury Shows Sexual Dimorphism in Functional Recovery and Cardio-Metabolic Responses

Abstract After spinal cord injury (SCI), emergency treatment intervention can minimize tissue damage, which is closely related to the recovery of long-term function. Here, we examined whether the administration of a single dose of riluzole (6 mg/kg) immediately after SCI was a critical window for the drug to exert its regulatory effect and limit long-term neurological deficits. The animals were sacrificed 1 day after administration for investigation of neuronal survival and a potential neuroinflammatory response, and sacrificed in the 6th week for assessment of neurological function. Riluzole applied in a single dose immediately post-SCI decreased the mRNA level of interleukin-1β at 6 h, reduced the destruction of neurons, and reduced the activation of microglia/macrophage M1 expression at day 1 post-SCI. Additionally, riluzole-treated rats showed higher expressions of interleukin-33 and its receptor ST2 in microglia/macrophages of the spinal cord than vehicle-treated rats, suggesting that this signaling pathway might be involved in microglia/macrophage-mediated inflammation. At 6 weeks, riluzole-treated rats exhibited higher motor function scores than vehicle-treated controls. In addition, riluzole-treated rats exhibited higher expression of GAP43 protein and shorter N1 peak latency and larger N1-P1 amplitude in motor-evoked potentials, compared to vehicle-treated rats. Together, these data suggested that early application of riluzole after SCI could be crucial for long-term functional recovery, so it may represent a promising therapeutic candidate within the critical therapeutic window for acute SCI.

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The influence of age on functional recovery of adults with spinal cord injury or disease after inpatient rehabilitative care: a pilot study

Aging Clinical and Experimental Research ◽

10.1007/s40520-013-0066-1 ◽

2013 ◽

Vol 25 (4) ◽

pp. 463-471 ◽

Cited By ~ 14

Author(s):

Julio C. Furlan ◽

Sander L. Hitzig ◽

B. Catharine Craven

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Pilot Study ◽

Functional Recovery ◽

Rehabilitative Care ◽

Cord Injury

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Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: Long-term survival and functional recovery in canines

Science China Life Sciences ◽

10.1007/s11427-019-1623-5 ◽

2020 ◽

Vol 63 (12) ◽

pp. 1879-1886

Author(s):

He Shen ◽

Shuyu Wu ◽

Xi Chen ◽

Bai Xu ◽

Dezun Ma ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Functional Recovery ◽

Term Survival ◽

Long Term Survival ◽

Cord Injury ◽

Adult Spinal Cord

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Long-term effects of an intensive interventional training program based on activities for individuals with spinal cord injury: a pilot study

Physiotherapy Theory and Practice ◽

10.3109/09593985.2015.1070938 ◽

2015 ◽

Vol 31 (8) ◽

pp. 568-574 ◽

Cited By ~ 3

Author(s):

Natalia Padula ◽

Mariana Costa ◽

Alexsandro Batista ◽

Roberta Gaspar ◽

Camilo Motta ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Pilot Study ◽

Training Program ◽

Long Term Effects ◽

Cord Injury

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Spleen tyrosine kinase facilitates neutrophil activation and worsens long-term neurologic deficits after spinal cord injury

Journal of Neuroinflammation ◽

10.1186/s12974-021-02353-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Dylan A. McCreedy ◽

Clare L. Abram ◽

Yongmei Hu ◽

Sun Won Min ◽

Madison E. Platt ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cell Death ◽

White Matter ◽

Functional Recovery ◽

Barrier Disruption ◽

Neurologic Deficits ◽

Cord Injury ◽

Blood Spinal Cord Barrier

Abstract Background Spinal cord injury elicits widespread inflammation that can exacerbate long-term neurologic deficits. Neutrophils are the most abundant immune cell type to invade the spinal cord in the early acute phase after injury, however, their role in secondary pathogenesis and functional recovery remains unclear. We have previously shown that neutrophil functional responses during inflammation are augmented by spleen tyrosine kinase, Syk, a prominent intracellular signaling enzyme. In this study, we evaluated the contribution of Syk towards neutrophil function and long-term neurologic deficits after spinal cord injury. Methods Contusive spinal cord injury was performed at thoracic vertebra level 9 in mice with conditional deletion of Syk in neutrophils (Sykf/fMRP8-Cre). Hindlimb locomotor recovery was evaluated using an open-field test for 35 days following spinal cord injury. Long-term white matter sparing was assessed using eriochrome cyanide staining. Blood-spinal cord barrier disruption was evaluated by immunoblotting. Neutrophil infiltration, activation, effector functions, and cell death were determined by flow cytometry. Cytokine and chemokine expression in neutrophils was assessed using a gene array. Results Syk deficiency in neutrophils improved long-term functional recovery after spinal cord injury, but did not promote long-term white matter sparing. Neutrophil activation, cytokine expression, and cell death in the acutely injured spinal cord were attenuated by the genetic loss of Syk while neutrophil infiltration and effector functions were not affected. Acute blood-spinal cord barrier disruption was also unaffected by Syk deficiency in neutrophils. Conclusions Syk facilitates specific neutrophil functional responses to spinal cord injury including activation, cytokine expression, and cell death. Long-term neurologic deficits are exacerbated by Syk signaling in neutrophils independent of acute blood-spinal cord barrier disruption and long-term white matter sparing. These findings implicate Syk in pathogenic neutrophil activities that worsen long-term functional recovery after spinal cord injury.

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