Remote ischemic conditioning improves outcome independent of anesthetic effects following shockwave-induced traumatic brain injury

Abstract

Traumatic brain injury due to primary blast exposure is a major cause of ongoing neurological and psychological impairment in soldiers and civilians. Animal and human evidence suggests that low-level blast exposure is capable of inducing white matter injury and behavioural deficits. There are currently no effective therapies to treat the underlying suspected pathophysiology of low-level primary blast or concussion. Remote ischemic conditioning (RIC) has been shown to have cardiac, renal and neuro-protective effects in response to brief cycles of ischemia. Here we examined the effects of RIC in two models of blast injury. We used a model of low-level primary blast in rats to evaluate the effects of RIC neurofilament expression. We subsequently used a model of traumatic brain injury in adult zebrafish using pulsed high intensity focused ultrasound (pHIFU) to evaluate the effects of RIC on behavioural outcome and apoptosis in a post-traumatic setting. In blast exposed rats, RIC pretreatment modulated NF200 expression suggesting an innate biological buffering effect. In zebrafish, behavioural deficits and apoptosis due to pHIFU-induced brain injury were reduced following administration of serum derived from RIC rats. The results in the zebrafish model demonstrate the humoral effects of RIC independent of anesthetic effects that were observed in the rat model of injury. Our results indicate that RIC is effective in improving outcome following modeled brain trauma in pre- and post-injury paradigms. The results suggest a potential role for innate biological systems in the protection against pathophysiological processes associated with impairment following shockwave induced trauma.

Effect of remote ischemic conditioning on the immune-inflammatory profile in patients with traumatic hemorrhagic shock in a randomized controlled trial

“…Therefore, future trials on RIC might focus on pre-hospital application of RIC or try to standardize the intervention by applying RIC as soon as patients arrive to the trauma bay. One interesting patient population might be soldiers at risk of traumatic injuries who may have RIC applied prophylactically (preconditioning) during pre-deployment 41 . Any of these strategies might serve to maximize RIC’s protective effect.…”

Study design for a randomized clinical trial of cognitive-behavioral therapy for posttraumatic headache

“…Military veterans are more likely than civilians to experience head injury associated with blast exposure (i.e., barotrauma) or overpressure associated with discharge of firearms. Some suggest that barotrauma may have unique effects on the brain that could result in characteristically different rates and presentations of headache [ 73 ], though the body of research is equivocal, with some reporting evidence that head injury mechanisms have little differential impact on brain functioning [ 74 ]. Unfortunately, the body of literature describing unique contributions of barotrauma to TBI (and TBI-related headache) is sparse and does not provide enough information to lead to a reasonable stratification of head injury type (i.e., barotrauma versus blunt trauma).…”