نقش سیگنالینگ JAK-STAT در بازیابی کارایی حرکتی بعد از آسیب دیدگی نخاعی (SCI)

ABSTRACT Role of JAK-STAT Signalling on Motor Function Recovery after Spinal Cord Injury

Worldwide, an estimate of 180,000 cases of spinal cord injuries (SCI) occur yearly [1]. SCI results in the complete or partial loss of motor and sensory functions below the lesion site. This type of injury causes irreversible paralysis, chronic pain, loss of bladder, bowel and sexual function, amongst others dysfunctions, impairing quality and increasing the cost of life [2, 3].

The pathology of SCI in mammals starts with an acute phase during the first days of injury, which includes massive cell death and inflammatory response. The acute response is followed by a second phase during the first week after injury consisting of tissue replacement, where the loss of cells is replaced by a glial scar. After the second week it finalizes with a third phase which continues for months involving chronic tissue remodelling, remyelination and circuit remodelling [4]. Although some spontaneous repair after SCI has been described in mammals including humans, it contributes poorly to motor and functional recovery. Progenitor cells proliferate and differentiate but mostly to glial cells while no neurogenesis occurs [5, 6]. Besides there is only a partial axon regeneration and circuit remodelling response that contribute to a limited compensatory recovery [2].

Several reviews have been published describing growth factors and cytokines that regulate cell response in SCI [2, 7, 8]. Advancements using these factors to improve spinal cord repair are being made, and preclinical treatments have been achieved by local delivery of growth factors and by physiological delivery with i.v. or i.p. injections (intravenous or intraperitoneal, respectively) [2]. Between the plethora of signalling pathways activated in response to tissue injury, the JAK-STAT signalling pathway is one of the main pathways that has been extensively studied because of its broad effect on the response to injury. In this chapter, we discuss the activation and role of JAK-STAT signalling in response to SCI and studies focused on modulating JAK-STAT to improve motor recovery. First, we briefly describe the JAK-STAT pathway components, followed by a discussion of its role in different cellular processes including: axonal regeneration, neuroprotection, glial response and its effects on the inflammatory response.