The brain-derived neurotrophic factor Val66Met polymorphism and degeneration of the corticospinal tract after stroke: a diffusion tensor imaging study

Eur J Neurol. 2016 Jan;23(1):76-84. doi: 10.1111/ene.12791. Epub 2015 Jul 31.

Abstract

Background and purpose: A common single nucleotide polymorphism, Val66Met, in the human brain-derived neurotrophic factor (BDNF) gene has a potential role in the pathogenesis and treatment of stroke. The relevance of the BDNF Val66Met polymorphism to long-term stroke outcomes was examined, specifically with respect to changes in corticospinal integrity.

Methods: Thirty-five stroke patients with unilateral motor weakness were genotyped within 2 weeks after onset (T1), and changes in the integrity of the ipsilesional corticospinal tract (CST) as well as alterations in motor function at 1 month (T2) and 3 months after onset (T3) were tracked.

Results: On the basis of the Fugl-Meyer assessment upper extremity score, carriers of the Met allele (Val/Met and Met/Met) showed poorer motor outcomes at T2 and T3 compared to carriers of only the Val allele (Val/Val). For both BDNF allele types, patients exhibited characteristic degeneration of the CST compared to healthy controls. There were no differences between the two genotypes with respect to time-dependent changes in diffusion-tensor-imaging-derived parameters of the CST. However, the two groups showed different relationships between motor outcomes and directional diffusivities according to the elapsed time after onset. Poorer motor function was associated with lower axial diffusivity values for the Val/Val genotype group in the sub-acute phase (T1 and T2) but with higher radial diffusivity values for the Val/Met and Met/Met genotype group in the early chronic phase (T3).

Conclusions: Motor recovery in stroke patients may be affected by the BDNF Val66Met polymorphism, possibly through its effects on distinct pathological processes underlying corticospinal degeneration.

Keywords: brain-derived neurotrophic factor; diffusion tensor imaging; motor skills; pyramidal tracts; recovery of function; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain-Derived Neurotrophic Factor / genetics*
  • Diffusion Tensor Imaging
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Pyramidal Tracts / pathology*
  • Recovery of Function / genetics*
  • Stroke / genetics*
  • Stroke / pathology
  • Stroke / physiopathology

Substances

  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human