Peggy Nguyen, MD

Cui X, Chopp M, Zacharek A, Cui C, Yan T, Ning R, and Chen J. D-4F Decreases White Matter Damage After Stroke in Mice. Stroke. 2016

D-4F, an apolipoprotein analogue, has been studied as a potential therapy in the treatment of atherosclerosis. Prior studies suggest that D-4F may enhance HDL function, which could be potential target for neuroprotection in stroke. Here, the authors investigated the in vivo effect of D-4F on serum biomarkers, stroke outcome, inflammation and white matter recovery in a mouse stroke mode. Significantly, they found:

  • D-4F treatment at all dosages (2, 4, 8, 16 and 32 mg/kg daily for 7 days) had no significant effect on serum levels of HDL, total cholesterol, triglyceride and infarction volume but treatment at 16 mg/kg daily for 7 days did improve functional outcome after stroke as measured by the modified Neurological Severity Score (mNSS) at 7 days and as measured by the foot-fault test at 3 and 7 days after stroke.
  • D-4F treatment decreased white matter damage and increased oligodencrocyte progenitor cells after stroke. Accordingly, a better functional outcome (lower mNSS) significantly correlated with higher axonal density.
  • D-4F treatment decreased inflammatory markers TLR4 and TNFÎą but increased IGF1, which promotes neuronal and oligodendrocyte differentiation, proliferation, myelination and may serve as the pathway for via which D-4F treatment exerts its protective effects.

Both D-4F and IGF1 treatment of primary cortical neuron cultures in vitro increased neurite outgrowth significantly.

So far, none of the investigated neuroprotectants have been proven to be beneficial for stroke outcomes. Although this study is obviously limited by its subjects (being mouse models), the results show promise in identification of a possible neuroprotectant for stroke.

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