Reduction of PrPC in human cerebrospinal fluid after spinal cord injury

Carnini, Anna; Casha, Steve; Yong, V. Wee; Hurlbert, R. John; Braun, Janice E. A.

doi:10.4161/pri.4.2.11756

Cited by 10 publications

(11 citation statements)

References 48 publications

(59 reference statements)

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“…Previous studies have shown presence of immunoglobulins in mice or patients with SCI, but no data from sham or healthy controls were presented. 10,40,41 Increased immunoglobulins within the lesioned cervical cord at 2 weeks post-cSCI were seen in parallel with increased counts of ASCs in the spleen, suggesting that the spleen may be one of the sources of autoantibodies targeting the spinal cord. Other sources, such as the bone marrow and the regional lymph nodes that receive antigenic drainage from the spinal cord, 42 also could contribute to the pool of autoantibodies against the spinal cord in the subacute phase.…”

Section: Discussionmentioning

confidence: 98%

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Ulndreaj

Τζέκου

Mothe

et al. 2017

Journal of Neurotrauma

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The immune system plays a critical and complex role in the pathobiology of spinal cord injury (SCI), exerting both beneficial and detrimental effects. Increasing evidence suggests that there are injury level-dependent differences in the immune response to SCI. Patients with traumatic SCI have elevated levels of circulating autoantibodies against components of the central nervous system, but the role of these antibodies in SCI outcomes remains unknown. In rodent models of mid-thoracic SCI, antibody-mediated autoimmunity appears to be detrimental to recovery. However, whether autoantibodies against the spinal cord are generated following cervical SCI (cSCI), the most common level of injury in humans, remains undetermined. To address this knowledge gap, we investigated the antibody responses following cSCI in a rat model of injury. We found increased immunoglobulin G (IgG) and IgM antibodies in the spinal cord in the subacute phase of injury (2 weeks), but not in more chronic phases (10 and 20 weeks). At 2 weeks post-cSCI, antibodies were detected at the injury epicenter and co-localized with the astroglial scar and neurons of the ventral horn. These increased levels of antibodies corresponded with enhanced activation of immune responses in the spleen. Higher counts of antibodysecreting cells were observed in the spleen of injured rats. Further, increased levels of secreted IgG antibodies and enhanced proliferation of T-cells in splenocyte cultures from injured rats were found. These findings suggest the potential development of autoantibody responses following cSCI in the rat. The impact of the post-traumatic antibody responses on functional outcomes of cSCI is a critical topic that requires further investigation.

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Section: Discussionmentioning

confidence: 98%

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Ulndreaj

Τζέκου

Mothe

et al. 2017

Journal of Neurotrauma

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“…This 12-hour window for intervention has been utilized, for example, in a recent prospective randomized trial of minocycline for acute SCI. 10 The timing of arrival at our level 1 trauma centre has a great deal to do with our geography and referral catchment area. The province of British Columbia, for which our hospital serves as the sole referral centre for acute SCI, spans a land area of over 360,000 square miles [9.32 Â 10 5 km 2 ] (roughly 35% larger than the state of Texas).…”

Section: How Many Patients With Acute Sci Do You See In a Year?mentioning

confidence: 99%

“…Even in the phase I minocycline trial, 10 it took almost five years for a single centre to recruit sufficient patient numbers. The most obvious solution to this is to perform multicenter controlled trials, which require a larger budget, close coordination, standardization of procedures and protocols, and the willingness of centres to commit their acute SCI population to studies which may be initiated and coordinated from other sites.…”

Section: How Many Patients With Acute Sci Do You See In a Year?mentioning

confidence: 99%

Feasibility of patient recruitment into clinical trials of experimental treatments for acute spinal cord injury

Lee

Noonan

Batke

et al. 2012

Journal of Clinical Neuroscience

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“…30,31 Efforts to elucidate the physiological role of PrPC in the CNS have determined its involvement in various functions, including cellular adhesion, cell signaling, ion homeostasis, and neuroprotection. [32][33][34][35][36][37][38][39][40][41][42][43][44] Because of PrPC's extracellular nature, it is possible that during blast exposure, shearing forces from the primary blast wave traversing across the brain may cause the tenuously bound PrPC to dislodge and collect within the systemic circulation. We addressed this hypothesis by subjecting adult male Sprague-Dawley (S-D) rats to controlled single pulse shockwaves closely simulating free field blast and collecting blood plasma afterwards for quantification of PrPC.…”

Section: Introductionmentioning

confidence: 99%

Primary Blast-Induced Traumatic Brain Injury in Rats Leads to Increased Prion Protein in Plasma: A Potential Biomarker for Blast-Induced Traumatic Brain Injury

Pham

Sawyer²,

Wang³

et al. 2015

Journal of Neurotrauma

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Traumatic brain injury (TBI) is deemed the ''signature injury'' of recent military conflicts in Afghanistan and Iraq, largely because of increased blast exposure. Injuries to the brain can often be misdiagnosed, leading to further complications in the future. Therefore, the use of protein biomarkers for the screening and diagnosis of TBI is urgently needed. In the present study, we have investigated the plasma levels of soluble cellular prion protein (PrPC) as a novel biomarker for the diagnosis of primary blast-induced TBI (bTBI). We hypothesize that the primary blast wave can disrupt the brain and dislodge extracellular localized PrPC, leading to a rise in concentration within the systemic circulation. Adult male Sprague-Dawley rats were exposed to single pulse shockwave overpressures of varying intensities (15-30 psi or 103.4-206.8 kPa] using an advanced blast simulator. Blood plasma was collected 24 h after insult, and PrPC concentration was determined with a modified commercial enzyme-linked immunosorbent assay (ELISA) specific for PrPC. We provide the first report that mean PrPC concentration in primary blast exposed rats (3.97 ng/mL -0.13 SE) is significantly increased compared with controls (2.46 ng/mL -0.14 SE; two tailed test p < 0.0001). Furthermore, we report a mild positive rank correlation between PrPC concentration and increasing blast intensity (psi) reflecting a plateaued response at higher pressure magnitudes, which may have implications for all military service members exposed to blast events. In conclusion, it appears that plasma levels of PrPC may be a novel biomarker for the detection of primary bTBI.

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Reduction of PrPC in human cerebrospinal fluid after spinal cord injury

Cited by 10 publications

References 48 publications

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Characterization of the Antibody Response after Cervical Spinal Cord Injury

Feasibility of patient recruitment into clinical trials of experimental treatments for acute spinal cord injury

Primary Blast-Induced Traumatic Brain Injury in Rats Leads to Increased Prion Protein in Plasma: A Potential Biomarker for Blast-Induced Traumatic Brain Injury

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