Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

Abstract

Differential astroglial responses in the spinal cord of rats -ORIGINAL ARTICLE NeuroregenerationDifferential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract. Implications on cell therapy for nerve repair 1 Respostas astrocitárias na medula espinal do rato submetido ao esmagamento duplo do nervo ciático e tratado com injeção local de suspensão de células de Schwann cultivadas ou de extrato de medula espinal lesada. Implicações na terapia celular para o reparo do nervo ABSTRACT Purpose: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC), a peripheral glia, also react after nerve lesion favoring wound/repair, fi ber outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. Methods: Injections of a cultured SC suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. Local injection of phosphate buffered saline (PBS) served as control. One week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantifi ed by means of quantitative image analysis. Results: In the ipsilateral ventral horn, slight astroglial activations were seen after PBS or SC injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. Moreover, SC suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. Conclusion: Spinal cord astrocytes react according to repair processes of axotomized nerve, which may infl uence the functional outcome. The event should be considered during the neurosurgery strategies. Key words: Sciatic nerve lesion. Astrocyte. Neuronal protection. Neuroplasticity. Neuroregeneration. Pain. Review. RESUMOObjetivo: Astrócitos reativos participam de vários mecanismos após lesões do sistema nervoso central e periférico, os quais incluem neuroproteção, brotamento neuronal, neurotransmissão e dor neuropática. As células de Schwann (CS), um tipo de glia periférica, também reagem com a lesão do nervo, podendo interferir com o reparo e cicatrização, crescimento de fi bras e regeneração neuronais. Investigamos aqui a possibilidade da terapia celular para o reparo do nervo ciático poder alterar o padrão da ativação astrocitária nos cornos anterior e posterior da medula espinal do rato. Métodos: Suspensão de CS cultivadas ou extrato homogeneizado de medula espinal lesada de rato foram inoculados num reservatório feito a partir de dois esmagamentos aplicados no nervo ciático do rato distantes 0,5mm entre si. Injeção local de salina t...

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

“…Our findings of increased GFAP immunoreactivity in the facial nucleus following crush or transection lesions of facial nerve are in agreement and extend previous observations which have described retrograde astroglial reactivity after axotomy of cranial motoneurons [15] and also lesions of spinal nerves containing sensory and motor fibers [18,45].…”

“…The retrograde phenomenon following axotomy was also observed by the astrocytic reaction in the injured facial nuclei. Activation of astrocytes has been demonstrated after neuronal lesion [ 45 ], electrical stimulation [ 46 ], cytokine administration [ 47 ] by means of the increases of GFAP immunoreactivity or mRNA. The astrocytic activation has been described to be related to local ionic homeostasis as well as to production of neurotrophic factors [ 48 ].…”

S100ß and fibroblast growth factor-2 are present in cultured Schwann cells and may exert paracrine actions on the peripheral nerve injury

“…Neurotrophic factors produced by satellite cells and Schwann cells are the key molecules in the mechanisms of peripheral neuronal development, maintenance, function and regeneration 7,15 . S100ß immunoreactivity has been used as a marker for Schwann cells in vivo and in vitro 27,28 and also for the satellite cells in vivo 7 .…”

“…Rats (n=5) were anaesthetized with sodium pentobarbital 3% (38 mg/kg, ip) and submitted to an unilateral crush (Figure 1) of the sciatic nerve as described elsewhere 15 . The proximal stump of the sciatic nerve was studied and contralateral unoperated side was used as control.…”

Sagittal spinal alignment in paraplegics: a new paradigm for the rehabilitation under neuromuscular electrical stimulation

“…1 Current technology is allowing one to catch glimpses of the beginnings of a new dimension in the treatment of patients with spinal cord injury: (1) functional rehabilitation, where paraplegics are standing and sauntering under electrical stimuli 2,3 and (2) the attempt to regenerate the injured spinal cord tissue. 4 Rehabilitation programs offer these patients the acquisition of postural reorientation from the use of the intact residual sensory-motor system, above the neurological damage. 5 Potten et al 6 and Seelen et al 7 observed that in paraplegics, the loss of function of the erector spinae muscle is partially offset by an increase in electromyographic activity and hypertrophy of the latissimus dorsi and the upper third of the trapezius muscles.…”