Differential cellular FGF-2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell’s palsy

Abstract

BackgroundThe etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2) pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system.MethodsAdult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave) or systemic corticosterone (10 mgkg-1). Animals were sacrificed seven days later.ResultsCrush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection) and nuclear FGF-2 (57% after transection) in astrocytes (confirmed by two-color immunoperoxidase) in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction.ConclusionFGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell's palsy.

Electrical Stimulation Promotes Wound Healing by Enhancing Dermal Fibroblast Activity and Promoting Myofibroblast Transdifferentiation

“…ES was shown to enhance cell proliferation by increasing the cyclic AMP content (cAMP) and by stimulating gap-junction communication [39]. It has been previously reported that ES led to elevation of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes [40]. Also, Düsterhöft et al reported that ES modulates the expression level of FGF-1, FGF-2 and their receptors (FGFR1, FGFR4) in the tibialis anterior muscle of hypothyroid rat, as well as in satellite cell cultures derived from normal rat [41].…”

Central Facial Nervous System Biomolecules Involved in Peripheral Facial Nerve Injury Responses and Potential Therapeutic Strategies

“…As first responders to injury, VIP and PS help resolve acute inflammatory processes and inhibit the induction of TNFα and IL-6 in CNS microglia, which reduces neuronal loss around the lesion site [58]. FGF-2 plays an important role in tissue development and damage repair, increasing the number of GFAP-positive astrocytes in the facial nucleus after facial nerve injury and enhancing their expression of FGF-2 [59,93]. FGF-2 promotes the survival of injured neurons and preserves synaptic plasticity and neurotransmitter release, which are crucial for neuroprotection [88].…”

“…Axotomy increases the number of GFAP-positive astrocytes in the facial nucleus and enhances their nuclear expression of FGF-2. The resulting increase in FGF-2 in the cytoplasm of reactive astrocytes leads to enhanced secretion of FGF-2, which acts in a paracrine and autocrine manner to provide trophic support to the facial nucleus, thereby preventing Bell's palsy [59]. Astrocyte activation in the CNS after peripheral nerve injury contributes to nerve regeneration by maintaining immune homeostasis [97], reflecting the critical role of astrocytes in restoring the blood-brain barrier, providing neuroprotection, and limiting the proliferation of inflammatory cells [98].…”