Nerve regeneration and functional recovery by collagen-binding brain-derived neurotrophic factor in an intracerebral hemorrhage model

Tissue Eng Part A. 2015 Jan;21(1-2):62-74. doi: 10.1089/ten.TEA.2014.0139. Epub 2014 Sep 12.

Abstract

Brain-derived neurotrophic factor (BDNF) exerts therapeutic effects following intracerebral hemorrhage (ICH). However, it is difficult to maintain sufficient concentrations in the hemorrhage hemisphere. We demonstrated previously that BDNF fused to a collagen-binding domain (CBD) could bind to collagen in the ventricular ependyma and stimulate cell proliferation in the subventricular zone (SVZ). In this study, we verified the therapeutic effects of CBD-BDNF in the rat ICH model induced by bacterial collagenase by injecting CBD-BDNF into the lateral ventricle of ICH rats. The results demonstrated that CBD-BDNF was retained at high levels in the hemorrhage hemisphere, where it promoted neural regeneration and angiogenesis, reduced tissue loss, and improved functional recovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain / blood supply
  • Brain / metabolism
  • Brain / pathology
  • Brain Edema / complications
  • Brain Edema / drug therapy
  • Brain Edema / pathology
  • Brain Edema / physiopathology
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Brain-Derived Neurotrophic Factor / therapeutic use*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / physiopathology*
  • Collagen / metabolism*
  • Disease Models, Animal
  • Glucose / metabolism
  • Hematoma / complications
  • Hematoma / drug therapy
  • Hematoma / pathology
  • Hematoma / physiopathology
  • Hemodynamics / drug effects
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Male
  • Neovascularization, Physiologic / drug effects
  • Nerve Regeneration* / drug effects
  • Neurogenesis / drug effects
  • Positron-Emission Tomography
  • Protein Binding / drug effects
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use*
  • Recovery of Function* / drug effects
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Brain-Derived Neurotrophic Factor
  • Recombinant Fusion Proteins
  • Collagen
  • Glucose