Low Circulating Acute Brain-Derived Neurotrophic Factor Levels Are Associated With Poor Long-Term Functional Outcome After Ischemic Stroke.
Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair, and it influences stroke outcomes in animal models. Circulating BDNF concentrations are lowered in patients with traumatic brain injury, and low BDNF predicts poor recovery after this injury. We sought to investigate whether circulating concentrations of BDNF are altered in the acute phase of ischemic stroke and whether they are associated with short- or long-term functional outcome.



Serum concentrations of BDNF were measured in the Sahlgrenska Academy Study on Ischemic Stroke. The main outcomes were modified Rankin Scale (mRS) good (mRS score of 0-2) versus poor (mRS score of 3-6) at 3 months and 2 years after stroke, and good (mRS score of 0-2) versus poor (mRS score of 3-5) at 7 years after stroke.



Acute concentrations of BDNF were significantly lower in ischemic stroke cases (n=491) compared with controls (n=513). BDNF concentrations were not significantly associated with 3-month outcome. However, patients with BDNF in the lowest tertile had an increased risk of experiencing a poor outcome both at 2-year and 7-year follow-up, and these associations were independent of vascular risk factors and stroke severity (odds ratio, 2.6; confidence intervals, 1.4-4.9; P=0.002 and odds ratio, 2.1; confidence intervals, 1.1-3.9; P=0.028, respectively).



Circulating concentrations of BDNF protein are lowered in the acute phase of ischemic stroke, and low levels are associated with poor long-term functional outcome. Further studies are necessary to confirm these associations and to determine the predictive value of BDNF in stroke outcomes.
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.). tara.stanne@gu.se.
Tara M
TM
Stanne
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
N David
ND
Åberg
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
Staffan
S
Nilsson
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
Katarina
K
Jood
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
Christian
C
Blomstrand
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
Ulf
U
Andreasson
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
Kaj
K
Blennow
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
Henrik
H
Zetterberg
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
Jörgen
J
Isgaard
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
Johan
J
Svensson
From the Department of Medical and Clinical Genetics (T.M.S., C.J.), Department of Internal Medicine (NDÅ, J.I., J.S.), Center of Brain Repair and Rehabilitation (N.D.Å., C.B.), Department for Clinical Neuroscience and Rehabilitation (K.J., C.B.), Department of Psychiatry and Neurochemistry (U.A., K.B., H.Z.), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Mathematical Sciences, Gothenburg, Sweden (S.N.); and UCL Institute of Neurology, London, United Kingdom (H.Z.).
Christina
C
Jern
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D001925:Brain Damage, Chronic / Q000097:blood / Q000209:etiology; D002545:Brain Ischemia / Q000097:blood* / Q000628:therapy; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D012372:ROC Curve; D020127:Recovery of Function; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
brain-derived neurotrophic factor; pathogenesis; risk factors; serum; stroke