Basic Fibroblast Growth Factor (bFGF) Enhances Tissue Sparing and Functional Recovery Following Moderate Spinal Cord Injury

Abstract

The rapid increase in basic fibroblast growth factor (bFGF) production following spinal cord injury (SCI) in rats is thought to serve a role in the cellular processes responsible for the functional recovery often observed. In this study, bFGF was intrathecally administered continuously for 1 week beginning 30 min after a moderate (12.5 mm) spinal cord contusion in adult rats using the New York University impactor device. Osmotic minipumps were implanted into the lateral ventricle and lumbar thecal sac to deliver bFGF at a rate of 3 microg or 6 microg per day versus control vehicle. Animals were behaviorally tested for 6 weeks using the Basso, Beattie, Bresnahan locomotor rating scale and histologically assessed for both tissue sparing and glial reactivity rostral and caudal to the lesion. Rats treated with bFGF regained coordinated hindlimb movements earlier than controls and demonstrated consistent coordination from 4 to 6 weeks. Vehicle-treated rats showed only modest improvements in hindlimb function. The amount of spared tissue was significantly higher in bFGF-treated rats than in controls. Astrocyte and microglial reactivity was more pronounced in bFGF-treated animals versus controls. In summary, intrathecal infusion of exogenous bFGF following SCI significantly reduces tissue damage and enhances functional recovery. Early pharmacological intervention with bFGF following SCI may serve a neuroprotective role and/or create a proregenerative environment, possibly by modulating the neuroglial response.

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

“…Administration of exogenous growth factors following SCI promotes functional recovery [17,18]; intrathecal administration of bFGF also significantly enhances functional recovery after moderate and severe contusions in SCI rats [19,20], but the precise mechanism underlying the observed therapeutic effects has not been elucidated. In our latest studies, bFGF was demonstrated to inhibit excessive autophagy and endoplasmic reticulum stress in SCI, which contributed to functional recovery [21,22].…”

“…However, although abundant evidence suggests that bFGF has a therapeutic effect on SCI in rats [19,22,51], there has been no clinical trial investigating this. In acute stroke, a 24-h intravenous infusion of 5 mg bFGF has been confirmed as safe for patients and results in an improved outcome [52].…”

Protective effects of oral creatine supplementation on spinal cord injury in rats

“…4 These cells could be responsible for axonal demyelination and further functional impairment. 3,4,9 Considering the protective e ects of the energy precursor creatine on metabolically stressed neural cells in vitro, 18 it is likely that higher intracellular energy levels reached after creatine supplementation in vivo may have saved some of these cells in the penumbra zone around the primary lesion. Rescuing oligodendrocytes and preservation of myelin is expected to have large e ects on the functional outcome after SCI.…”

“…2,4 ± 7 The early phase of secondary tissue destruction a ects neuronal as well as glial cell populations. 2,4,8,9 Later, a dense gliotic scar develops, inhibiting axon regeneration in addition to the endogenously present myelinassociated neurite growth inhibitory constituents. 2,10 Although di erent glial cells participate in the scar formation, the reactive astrocytes play a predominant role re¯ected by the very high levels of glial acid ®brillary protein (GFAP).…”

Post-traumatic inflammation following spinal cord injury

“…80 Rescuing oligodendrocytes and preservation of myelin are expected to have large effects on the functional outcome after SCI. 16,63,89 Recently, using the anti-ssDNA monoclonal antibody F7-26 (Apostatin), it has been demonstrated that systemic administration of dexamethasone decreases apoptosis-related cell death in the injured spinal cord. 90 Wallerian degeneration and demyelination Apoptosis of oligodendrocytes leads to chronic demyelination thus causing anterograde neurodegeneration.…”