Effects of traumatic brain injury on blood pressure regulation and cardio-renal function in rats

Abstract

Traumatic Brain Injury (TBI) affects around 68 million people worldwide annually. While the neurologic effects of TBI have been extensively studied, potential effects on the autonomic nervous system have received less attention, despite clinical observations of autonomic dysfunction. We therefore sought to develop a rat model of repeated traumatic brain injury to examine the effects on cardiovascular and renal regulation, and we hypothesized that TBI would result in autonomic dysregulation of cardio-renal function. TBI was induced in male rats (250-300 gBW) under brief isoflurane anesthesia by dropping a 245g weight from a height of 1-1.5 meters onto the mid-sagittal area of the skull while the rat was suspended on a perforated tear-away platform. In the first series of experiments, blood pressure was measured continuously by telemetry over a two-week period, while rats were subjected to three successive injuries, each separated by 48 hours (repeated TBI, rTBI). Mean blood pressure was found to increase by about 7 mmHg following the third TBI (104.0 ± 1.1 to 111.0 ± 1.3 mmHg; p < 0.001, n=9). Though mild, the elevation in blood pressure was highly consistent, occurring in all of the injured rats. There were no correlate changes in heart rate observed in these rats. We then sought to examine the underlying causes of these blood pressure changes. Balance studies were performed using metabolic cages to examine salt and water intake and output before and during rTBI. Though intake of food and water were slightly affected by rTBI, no measurable effect of rTBI was observed on salt and water balance in these rats. We next measured cardiac function in anesthetized rats following rTBI and found no significant differences in any major contractile variables (LV systolic pressure, dP/tmax, dP/dtmin). In a final series of experiments, we evaluated renal blood flow during step-wise reductions in renal perfusion pressure using an aortic clamp and found that, while blood flow autoregulation was not impaired in rTBI rats, baseline renal blood flow was mildly reduced in injured rats compared to uninjured controls (3.44 ± 0.16 vs 3.94 ± 0.05 mL/min/gKW). In summary, we have generated a rat model of repeated traumatic brain injury that results in a consistent elevation of resting arterial blood pressure. Speculation that these observed changes may result from autonomic dysregulation remains to be investigated. University of Cincinnati College of Medicine Innovation Seed Grant This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.