Abstract
Following traumatic brain injury (TBI), ischemia and hypoxia play a major role in further worsening of the damage, a process referred to as ‘secondary injury’. Protecting neurons from causative factors of secondary injury has been the guiding principle of modern TBI management. Stimulation of trigeminal nerve induces pressor response and improves cerebral blood flow (CBF) by activating the rostral ventrolateral medulla. Moreover, it causes cerebrovasodilation through the trigemino-cerebrovascular system and trigemino-parasympathetic reflex. These effects are capable of increasing cerebral perfusion, making trigeminal nerve stimulation (TNS) a promising strategy for TBI management. Here, we investigated the use of electrical TNS for improving CBF and brain oxygen tension (PbrO2), with the goal of decreasing secondary injury. Severe TBI was produced using controlled cortical impact (CCI) in a rat model, and TNS treatment was delivered for the first hour after CCI. In comparison to TBI group, TBI animals with TNS treatment demonstrated significantly increased systemic blood pressure, CBF and PbrO2 at the hyperacute phase of TBI. Furthermore, rats in TNS-treatment group showed significantly reduced brain edema, blood-brain barrier disruption, lesion volume, and brain cortical levels of TNF-α and IL-6. These data provide strong early evidence that TNS could be an effective neuroprotective strategy.
Highlights
traumatic brain injury (TBI) is classified as either primary or secondary[1, 3,4,5,6]
We examined the effects of direct trigeminal nerve branch stimulation on mean arterial blood pressure (MAP), pulse pressure (PP), heart rate (HR), and respiration rate (RR) in naïve rats
PP and HR increased from 52 ± 9 to 57 ± 9 mmHg (p < 0.001 n = 12), and 340 ± 26 to 351 ± 26 bpm (p < 0.05 n = 12), respectively (Fig. 3C and D)
Summary
TBI is classified as either primary or secondary[1, 3,4,5,6]. The immediate mechanical destruction of the tissue and blood vessels that happens at the time of impact is the primary injury, and the damage is irreversible. In the critical early hours after trauma, the perilesional area becomes hypermetabolic, but at the same time there is a decrease in cerebral blood flow (CBF)[8,9,10,11,12,13] This mismatch of supply and demand leads to an energy crisis at the cellular level, resulting in additional death of neural tissue in the ischemic penumbra. TNS has been shown to decrease cerebrovascular resistance via the trigemino-cerebrovascular system[25] When activated, these pathways, via RVLM and trigemino-cerebrovascular system, can lead to significant increase in cerebral perfusion, making the trigeminal nerve a promising target in TBI management (Fig. 1). We showed that TNS was capable of decreasing brain edema, blood-brain barrier (BBB) disruption, lesion volume, and inflammatory response as evaluated by the levels of TNF-α and IL-6 in brain tissue
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