Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transections and induces remyelination

The extension of the lesion following spinal cord injury (SCI) poses a major challenge for regenerating axons, which must grow across several centimetres of damaged tissue in the absence of ordered guidance cues. Biofunctionalized electroconducting microfibres (MFs) that provide biochemical signals, as well as electrical and mechanical cues, offer a promising therapeutic approach to help axons overcome this blind journey. We used poly(3,4-ethylenedioxythiophene)-coated carbon MFs functionalized with cell adhesion molecules and growth factors to bridge the spinal cord after a partial unilateral dorsal quadrant lesion (PUDQL) in mice and followed cellular responses by intravital two-photon (2P) imaging through a spinal glass window. Thy1-CFP//LysM-EGFP//CD11c-EYFP triple transgenic reporter animals allowed real time simultaneous monitoring of axons, myeloid cells and microglial cells in the vicinity of the implanted MFs. MF biocompatibility was confirmed by the absence of inflammatory storm after implantation. We found that the sprouting of sensory axons was significantly accelerated by the implantation of functionalized MFs after PUDQL. Their implantation produced better axon alignment compared to random and misrouted axon regeneration that occurred in the absence of MF, with a most striking effect occurring two months after injury. Importantly, we observed differences in the intensity and composition of the innate immune response in comparison to PUDQL-only animals. A significant decrease of immune cell density was found in MF-implanted mice one month after lesion along with a higher ratio of monocyte-derived dendritic cells whose differentiation was accelerated. Therefore, functionalized carbon MFs promote the beneficial immune responses required for neural tissue repair, providing an encouraging strategy for SCI management.

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How to Do It: Microsurgical DREZotomy for Pain After Brachial Plexus Injury: 2-Dimensional Operative Video

Operative Neurosurgery ◽

10.1093/ons/opaa380 ◽

2021 ◽

Author(s):

Manon Duraffourg ◽

Andrei Brinzeu ◽

Marc Sindou

Keyword(s):

Spinal Cord ◽

Pain Relief ◽

Brachial Plexus ◽

Dorsal Horn ◽

Brachial Plexus Injury ◽

Dorsal Column ◽

Motor Deficit ◽

Complete Disappearance ◽

Burning Pain ◽

Root Entry Zone

Abstract More than three-quarters of victims of brachial plexus injury suffer from refractory neuropathic pain.1-6 Main putative mechanism is paroxysmal hyperactivity in the dorsal horn neurons at the dorsal root entry zone (DREZ) as demonstrated by microelectrode recordings in animal models7 and patients.8 Pain relief can be achieved by lesioning the responsible neurons in the spinal cord segments with avulsed rootlets.9,10 This video illustrates the technique for microsurgical DREZotomy.11,12 A C3-C7 hemilaminectomy is performed to access the C4-Th1 medullary segments. After opening the dura and arachnoid, and freeing the cord from arachnoid adhesions, the dorsolateral sulcus is identified. Identification can be difficult when the spinal cord is distorted and/or has a loss of substance. The dorsolateral sulcus is then opened with a microknife, so that microcoagulations are performed: 4 mm deep, at 35° angle in the axis of the dorsal horn, every millimeter in a dotted fashion along the avulsed segments. Care should be taken not to damage the corticospinal tract, laterally, and the dorsal column, medially. The patient consents to the procedure. In the presented case, surgery led to complete disappearance of the paroxysmal pain and reduced the background of burning pain to a bearable level without the need of opioid medication. There was no motor deficit or ataxia in the ipsilateral lower limb postoperatively. According to Kaplan-Meier analysis at 10 yr follow-up, in our overall series, microsurgical DREZotomy achieved total pain relief without any medication in 60% of patients, and in 85% without the need for opioids.10,13-15 Microelectrode recording at 1:26 reproduced from Guenot et al7 with permission from JNSPG.

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

Journal of Clinical Medicine ◽

10.3390/jcm9041221 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1221 ◽

Cited By ~ 3

Author(s):

Jacek M. Kwiecien ◽

Liqiang Zhang ◽

Jordan R. Yaron ◽

Lauren N. Schutz ◽

Christian J. Kwiecien-Delaney ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Tissue Damage ◽

Low Dose ◽

Dorsal Column ◽

Neurological Deficits ◽

Sustained Delivery ◽

Post Surgery ◽

Cord Injury ◽

Anti Inflammatory

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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Anti-amphiphysin antibody-positive paraneoplastic neurological syndrome with a longitudinally extensive spinal cord lesion of the dorsal column

Rinsho Shinkeigaku ◽

10.5692/clinicalneurol.54.572 ◽

2014 ◽

Vol 54 (7) ◽

pp. 572-576 ◽

Cited By ~ 1

Author(s):

Shuichiro Neshige ◽

Naoyuki Hara ◽

Shinichi Takeshima ◽

Hirotaka Iwaki ◽

Yutaka Shimoe ◽

...

Keyword(s):

Spinal Cord ◽

Paraneoplastic Neurological Syndrome ◽

Dorsal Column ◽

Spinal Cord Lesion ◽

Neurological Syndrome ◽

Cord Lesion

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