Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

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Recurrent spinal cord injury without radiographic abnormalities in children

Journal of Neurosurgery ◽

10.3171/jns.1988.69.2.0177 ◽

1988 ◽

Vol 69 (2) ◽

pp. 177-182 ◽

Cited By ~ 55

Author(s):

Ian F. Pollack ◽

Dachling Pang ◽

Robert Sclabassi

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Soft Tissues ◽

Spinal Cord Injuries ◽

Dorsal Column ◽

Neurological Deficits ◽

Spinal Instability ◽

Content Type ◽

Flexion Extension ◽

Cord Injury

✓ Spinal cord injury without radiographic abnormality is a well-known entity in the pediatric age group. Agerelated elasticity of the vertebral ligaments as well as immaturity of the osseous structures in the pediatric spine allow momentary subluxation in response to deforming forces. The resultant neurological injuries range from transient dorsal column dysfunction to complete cord transection. Between 1960 and 1985, 42 such injuries were treated at the Children's Hospital of Pittsburgh. Management of these radiographically occult spinal cord injuries consisted of cervical immobilization for 2 months in a hard collar and restriction of contact sports. Recurrent cord injury occurred in eight cases during the 2-month immobilization period. A clearly defined traumatic episode was identified in seven of the eight patients, although in four children the recurrent trauma to the spine was trivial. Five of the children removed their collars briefly before the second injury, and two children incurred reinjury with the hard collar in place. The remaining child was too young for hard-collar immobilization, and recurrent neurological deterioration occurred during sleep. Serial flexion-extension films failed to detect frank instability in any of the eight cases. The children most susceptible to reinjury were those who sustained mild or transient neurological deficits from an initial cord injury and who rapidly resumed normal activities. Radiographically occult spinal instability resulting from the initial injury to the vertebral and paravertebral soft tissues presumably made these children vulnerable to recurrent spinal cord injury, often from otherwise insignificant trauma. During the last 21 months, 12 additional children have been managed with a more stringent protocol combining neck immobilization in a rigid cervical brace for 3 months and restriction of both contact and noncontact sports, together with a major emphasis on patient compliance. With this new protocol, no recurrent cord injuries have been documented.

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Faculty Opinions recommendation of Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1001592.11054 ◽

2001 ◽

Author(s):

Marie Filbin

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Dorsal Column ◽

Lesion Site ◽

Cord Injury ◽

Adult Spinal Cord

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Rehabilitation of the canine patient following spinal cord injury: a practical guide

Companion Animal ◽

10.12968/coan.2020.0060 ◽

2021 ◽

Vol 26 (1) ◽

pp. 1-6

Author(s):

Cheryl Corral

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Spinal Injury ◽

Neurological Deficits ◽

Practical Guide ◽

Cord Injury ◽

Physical Therapies

This article forms part of a series exploring the rehabilitation of the canine shoulder, elbow, back, hip and stifle following injury or disease. Discussed here are different rehabilitation techniques used to address neurological deficits, pain and weakness following spinal injury, including physical therapies, electrotherapies and acupuncture.

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Beyond the lesion site: minocycline augments inflammation and anxiety-like behavior following SCI in rats through action on the gut microbiota

Journal of Neuroinflammation ◽

10.1186/s12974-021-02123-0 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Emma K. A. Schmidt ◽

Pamela J. F. Raposo ◽

Abel Torres-Espin ◽

Keith K. Fenrich ◽

Karim Fouad

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Spinal Cord Injury ◽

Nervous System ◽

Gut Microbiota ◽

Microglial Activation ◽

Motor Recovery ◽

Long Term Effects ◽

Cord Injury ◽

Anti Inflammatory

Abstract Background Minocycline is a clinically available synthetic tetracycline derivative with anti-inflammatory and antibiotic properties. The majority of studies show that minocycline can reduce tissue damage and improve functional recovery following central nervous system injuries, mainly attributed to the drug’s direct anti-inflammatory, anti-oxidative, and neuroprotective properties. Surprisingly the consequences of minocycline’s antibiotic (i.e., antibacterial) effects on the gut microbiota and systemic immune response after spinal cord injury have largely been ignored despite their links to changes in mental health and immune suppression. Methods Here, we sought to determine minocycline’s effect on spinal cord injury-induced changes in the microbiota-immune axis using a cervical contusion injury in female Lewis rats. We investigated a group that received minocycline following spinal cord injury (immediately after injury for 7 days), an untreated spinal cord injury group, an untreated uninjured group, and an uninjured group that received minocycline. Plasma levels of cytokines/chemokines and fecal microbiota composition (using 16s rRNA sequencing) were monitored for 4 weeks following spinal cord injury as measures of the microbiota-immune axis. Additionally, motor recovery and anxiety-like behavior were assessed throughout the study, and microglial activation was analyzed immediately rostral to, caudal to, and at the lesion epicenter. Results We found that minocycline had a profound acute effect on the microbiota diversity and composition, which was paralleled by the subsequent normalization of spinal cord injury-induced suppression of cytokines/chemokines. Importantly, gut dysbiosis following spinal cord injury has been linked to the development of anxiety-like behavior, which was also decreased by minocycline. Furthermore, although minocycline attenuated spinal cord injury-induced microglial activation, it did not affect the lesion size or promote measurable motor recovery. Conclusion We show that minocycline’s microbiota effects precede its long-term effects on systemic cytokines and chemokines following spinal cord injury. These results provide an exciting new target of minocycline as a therapeutic for central nervous system diseases and injuries.

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