Mechanisms implicated in the contralateral effect in the central nervous system after unilateral injury: focus on the visual system

Abstract

The retina, as part of the central nervous system is an ideal model to study the response of neurons to injury and disease and to test new treatments. During the last decade is becoming clear that unilateral lesions in bilateral areas of the central nervous system trigger an inflammatory response in the contralateral uninjured site. This effect has been better studied in the visual system where, as a rule, one retina is used as experimental and the other as control. Contralateral retinas in unilateral models of retinal injury show neuronal degeneration and glial activation. The mechanisms by which this adverse response in the central nervous system occurs are discussed in this review, focusing primarily on the visual system.

7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection

“…Moreover, DHF has been shown to have antioxidant activity and protect against glutamate induced excitotoxicitiy [ 100 ] or intravitreal injection of NMDA (Gallego-Ortega et al, unpublished observations), but whether this protection involves the same TrkB intracelular signalling pathways needs to be further investigated. Finally, optic nerve injury involves an inflammatory response in the injured and contralateral retina that is microglia mediated [ 32 , 101 ] and DHF has been shown to exert anti-inflammatory effects through microglia activation [ 102 , 103 ], thus it will be of interest to further correlate the role of microglial responses to fully understand the mechanisms of action of DHF.…”

Axonal Injuries Cast Long Shadows: Long Term Glial Activation in Injured and Contralateral Retinas after Unilateral Axotomy

“…We studied the course of glial cell activation after an unilateral optic nerve crush in mice, and show that glia from both injured and contralateral retinas react to the lesion. This bilateral response, the so-called contralateral effect, is being intensively studied in the visual system, and during the past decade more pieces were added to this puzzle [6,18,27,30,34,[40][41][42][43], the physiological mechanisms of which are still unknown (reviewed in [39,41]). Still, in all reports, the characteristics of this effect, postulated by Shenker et al (2003) [40], prevail: first, the damage must reach a minimal magnitude to elicit a contralateral response, and second, the response of the contralateral region is the same as that of the damaged one but attenuated in time and magnitude.…”

“…In the injured ones, their number increases linearly as the RGCs die with a parallel but opposed kinetics. In the uninjured retina, RGCs also die but their loss is very slow and does not progress further from 9 or 45 days (depending on the lesion site, see below [39,42]). Consequently, the number of transcellularly labelled MCs remains fairly constant.…”

“…Furthermore, these responses to ONC are not limited to the injured retina. Recently, it has been described that lesions do affect not only the injured retina but also the contralateral one-the so-called contralateral effect [39]. As theorised by [40], the uninjured contralateral retina responds as the injured one but in a subdued way showing, depending on the original insult, MC activation [11], phagocytic MC appearance [34], astrocyte and Müller cell activation [27,31,41], and loss of RGCs [42].…”

Ly6c as a New Marker of Mouse Blood Vessels: Qualitative and Quantitative Analyses on Intact and Ischemic Retinas

“…The contralateral effect is a puzzling phenomenon of yet unknown etiology, where the uninjured tissue/organ of a bilateral system responds to the injury performed in the other one (reviewed in [ 50 ]). Most current works on the contralateral response are described in the visual system.…”