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Published, Version of Record (VoR)Open Access Discount via Drexel Libraries Read and Publish Program 2026CC BY-NC-ND V4.0, Open
Journal article
Vascular integrity and immune infiltration in SCI pain: Can exercise tip the balance?
Experimental neurology, v 400, 115702
Jun 2026
PMID: 41734862
Featured in Collection : Drexel's Newest Publications
Abstract
Chronic neuropathic pain is a debilitating consequence of spinal cord injury (SCI), yet effective treatments remain limited. Exercise reduces pain incidence after SCI, but the underlying mechanisms linking vascular and immune regulation to pain resilience are unclear. Here, we investigated how aerobic exercise influences blood brain/spinal cord barrier (BBB/BSCB) integrity, vascular protein expression, and neuroimmune activation along the sensory neuroaxis. Female rats received unilateral cervical SCI or served as uninjured controls and were assigned to sedentary or forced wheel exercise groups. Behavioral testing revealed that exercise prevented SCI induced tactile allodynia and normalized avoidance of noxious stimuli. Using Evans Blue dye to assess BSCB permeability, we found that the blood spinal cord barrier was transiently disrupted after SCI but recovered by six weeks. Exercise restored expression of the tight junction protein occludin at the lesion epicenter, while the vascular marker CD13 remained stable. Cortical barrier proteins were unchanged, yet glial activation was regionally distinct: the anterior cingulate cortex (ACC) exhibited robust microglial and astrocytic reactivity not observed in the primary somatosensory cortex. Exercise reduced astrocytic reactivity in the ACC and normalized microglial activation below the lesion, indicating that its immune effects are spatially selective rather than global. Together, these findings demonstrate that post SCI exercise stabilizes tight junctions, limits maladaptive glial activation, and preserves vascular immune homeostasis across pain processing circuits. This work identifies the ACC as a uniquely reactive cortical site in SCI pain and highlights vascular resilience as a potential therapeutic target for preventing chronic pain.
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Details
- Title
- Vascular integrity and immune infiltration in SCI pain: Can exercise tip the balance?
- Creators
- Grace Giddings - Drexel University, Neurobiology and AnatomyMegan R Detloff (Corresponding Author) - Drexel University, Neurobiology and Anatomy
- Publication Details
- Experimental neurology, v 400, 115702
- Publisher
- Elsevier
- Number of pages
- 17
- Grant note
- National Institutes of Health NINDS: NS NIH NINDS R01 NS097880
Financial support was contributed by the National Institutes of Health NINDS R01 and H.E.A.L. Initiative Supplement NS NIH NINDS R01 NS097880 (MRD) . No potential competing interests was declared by the authors. We would like to acknowledge technical support and expertise provided by Jordan Dowtin-Dorsey, Theresa Connors, and Dr. Timothy Cunningham. We also gratefully acknowledge Dr. John Houle for thoughtful discussions and manuscript review.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:001706502700001
- Other Identifier
- 991022161141204721