title: Improvement of Impaired Cerebral Microcirculation Using Rheological Modulation by Drag-Reducing Polymers.
abstract: Nanomolar intravascular concentrations of drag-reducing polymers (DRP) have been shown to improve hemodynamics and survival in animal models of ischemic myocardium and limb, but the effects of DRP on the cerebral microcirculation have not yet been studied. We recently demonstrated that DRP enhance microvascular flow in normal rat brain and hypothesized that it would restore impaired microvascular perfusion and improve outcomes after focal ischemia and traumatic brain injury (TBI). We studied the effects of DRP (high molecular weight polyethylene oxide, 4000 kDa, i.v. at 2 μg/mL of blood) on microcirculation of the rat brain: (1) after permanent middle cerebral artery occlusion (pMCAO); and (2) after TBI induced by fluid percussion. Using in vivo two-photon laser scanning microscopy (2PLSM) over the parietal cortex of anesthetized rats we showed that both pMCAO and TBI resulted in progressive decrease in microvascular circulation, leading to tissue hypoxia (NADH increase) and increased blood brain barrier (BBB) degradation. DRP, injected post insult, increased blood volume flow in arterioles and red blood cell (RBC) flow velocity in capillaries mitigating capillary stasis, tissue hypoxia and BBB degradation, which improved neuronal survival (Fluoro-Jade B, 24 h) and neurologic outcome (Rotarod, 1 week). Improved microvascular perfusion by DRP may be effective in the treatment of ischemic stroke and TBI.
authors.affiliation: Department of Neurosurgery, University of New Mexico, Albuquerque, NM, USA. dbragin@salud.unm.edu.
authors.forename: D E
authors.initials: DE
authors.lastname: Bragin
authors.affiliation: Department of Neurosurgery, Central South University, Changsha, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, University of New Mexico, Albuquerque, NM, USA.
authors.forename: O A
authors.initials: OA
authors.lastname: Bragina
authors.affiliation: Department of Neurosurgery, University of New Mexico, Albuquerque, NM, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Statom
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Kameneva
authors.affiliation: Department of Neurosurgery, University of New Mexico, Albuquerque, NM, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Nemoto
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability; D015687:Cell Hypoxia; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D018056:Hemorheology / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D036641:Microscopy, Fluorescence, Multiphoton; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008970:Molecular Weight; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010296:Parietal Lobe / Q000098:blood supply*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D009243:NAD; D011092:Polyethylene Glycols; C000595214:polyethylene glycol 4000
keywords: Cerebral blood flow; Drag reducing polymers; Ischemia; Rheological modulation; Traumatic brain injury