Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats.
Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood-brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.
1 Department of Neurosurgery, School of Medicine, University of New Mexico, Albuquerque, NM, USA.
Denis E
DE
Bragin
2 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.|3 Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.|4 Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
Marina V
MV
Kameneva
1 Department of Neurosurgery, School of Medicine, University of New Mexico, Albuquerque, NM, USA.
Olga A
OA
Bragina
1 Department of Neurosurgery, School of Medicine, University of New Mexico, Albuquerque, NM, USA.
Susan
S
Thomson
1 Department of Neurosurgery, School of Medicine, University of New Mexico, Albuquerque, NM, USA.
Gloria L
GL
Statom
1 Department of Neurosurgery, School of Medicine, University of New Mexico, Albuquerque, NM, USA.
Devon A
DA
Lara
5 College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
Yirong
Y
Yang
1 Department of Neurosurgery, School of Medicine, University of New Mexico, Albuquerque, NM, USA.
Edwin M
EM
Nemoto
D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D012212:Rheology
D011108:Polymers; D011092:Polyethylene Glycols; D010100:Oxygen
Brain metabolism; cerebral blood microcirculation; drag-reducing polymers; rheology; traumatic brain injury