Traumatic brain injury (TBI) is frequently accompanied by hemorrhagic shock (HS) which significantly worsens morbidity and mortality. Existing resuscitation fluids (RF) for volume expansion inadequately mitigate impaired microvascular cerebral blood flow (mvCBF) and hypoxia after TBI/HS. We hypothesized that nanomolar quantities of drag reducing polymers in resuscitation fluid (DRP-RF), would improve mvCBF by rheological modulation of hemodynamics. Methods: TBI was induced in rats by fluid percussion (1.5 atm, 50 ms) followed by controlled hemorrhage to a mean arterial pressure (MAP) = 40 mmHg. DRP-RF or lactated Ringer (LR-RF) was infused to MAP of 60 mmHg for 1 h (pre-hospital), followed by blood re-infusion to a MAP = 70 mmHg (hospital). Temperature, MAP, blood gases and electrolytes were monitored. In vivo 2-photon laser scanning microscopy was used to monitor microvascular blood flow, hypoxia (NADH) and necrosis (i.v. propidium iodide) for 5 h after TBI/HS followed by MRI for CBF and lesion volume. Results: TBI/HS compromised brain microvascular flow leading to capillary microthrombosis, tissue hypoxia and neuronal necrosis. DRP-RF compared to LR-RF reduced microthrombosis, restored collapsed capillary flow and improved mvCBF (82 ± 9.7% vs. 62 ± 9.7%, respectively, p < 0.05, n = 10). DRP-RF vs LR-RF decreased tissue hypoxia (77 ± 8.2% vs. 60 ± 10.5%, p < 0.05), and neuronal necrosis (21 ± 7.2% vs. 36 ± 7.3%, respectively, p < 0.05). MRI showed reduced lesion volumes with DRP-RF. Conclusions: DRP-RF effectively restores mvCBF, reduces hypoxia and protects neurons compared to conventional volume expansion with LR-RF after TBI/HS.
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Supported by DOD DM160142, R21NS091600 and RMSE № 17.1223.2017/AP.
Manley G, Knudson MM, Morabito D et al (2001) Hypotension, hypoxia, and head injury: frequency, duration, and consequences. Arch Surg 136(10):1118–1123CrossRefPubMedGoogle Scholar
Navarro JC, Pillai S, Cherian L et al (2012) Histopathological and behavioral effects of immediate and delayed hemorrhagic shock after mild traumatic brain injury in rats. J Neurotrauma 29(2):322–334CrossRefPubMedGoogle Scholar
Bragin DE, Statom GL, Yonas H et al (2014) Critical cerebral perfusion pressure at high intracranial pressure measured by induced cerebrovascular and intracranial pressure reactivity. Crit Care Med 42(12):2582–2590CrossRefPubMedGoogle Scholar
Bragin DE, Kameneva MV, Bragina OA et al (2017) Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats. J Cereb Blood Flow Metab 37(3):762–775CrossRefPubMedGoogle Scholar
Kameneva MV, Wu ZJ, Uraysh A et al (2004) Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments. Biorheology 41(1):53–64PubMedGoogle Scholar
Fumagalli S, Coles JA, Ejlerskov P et al (2011) In vivo real-time multiphoton imaging of T lymphocytes in the mouse brain after experimental stroke. Stroke 42(5):1429–1436CrossRefPubMedGoogle Scholar
Kameneva MV (2012) Microrheological effects of drag-reducing polymers in vitro and in vivo. Int J Eng Sci 59:168–183CrossRefGoogle Scholar
Lee EJ, Hung YC, Lee MY (1999) Anemic hypoxia in moderate intracerebral hemorrhage: the alterations of cerebral hemodynamics and brain metabolism. J Neurol Sci 164(2):117–123CrossRefPubMedGoogle Scholar