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Review
. 2021 May:118:35-39.
doi: 10.1016/j.pediatrneurol.2021.01.011. Epub 2021 Feb 5.

Brain-Derived Neurotrophic Factor in Neonatal Seizures

Brennan J Sullivan  1 , Shilpa D Kadam  2
Affiliations
Review

Brain-Derived Neurotrophic Factor in Neonatal Seizures

Brennan J Sullivan et al. Pediatr Neurol. 2021 May.

Abstract

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has an extensively studied classical role in neuronal growth, differentiation, survival, and plasticity. Neurotrophic, from the Greek neuro and trophos, roughly translates as "vital nutrition for the brain." During development, BDNF and its associated receptor tyrosine receptor kinase B are tightly regulated as they influence the formation and maturation of neuronal synapses. Preclinical research investigating the role of BDNF in neurological disorders has focused on the effects of decreased BDNF expression on the development and maintenance of neuronal synapses. In contrast, heightened BDNF-tyrosine receptor kinase B activity has received less scrutiny for its role in neurological disorders. Recent studies suggest that excessive BDNF-tyrosine receptor kinase B signaling in the developing brain may promote the hyperexcitability that underlies refractory neonatal seizures. This review will critically examine BDNF-tyrosine receptor kinase B signaling in the immature brain, its role in the emergence of refractory neonatal seizures, and the potential of targeting BDNF-TrkB signaling as a novel antiseizure strategy.

Keywords: BDNF; Development; Epilepsy; KCC2; Seizures; TrkB.

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Conflict of interest statement

Conflict of Interest statement

SDK is listed as an author on US patent 10525024B2, “Methods for rescuing phenobarbital-resistance of seizures by ANA-12 or ANA-12 in combination with CLP290.”

Figures

Figure 1.
Figure 1.
Post-ischemic BDNF-TrkB signaling is proposed to facilitate the emergence of phenobarbital unresponsive neonatal seizures. (A) Schematized inhibitory synapses in a non-pathological neonatal brain, (B) post-ischemic insult, and (C) ANA12 treated post-ischemic insult. (D) Legend for proteins, molecules, and cell types of interest. An improved understanding of the multiples levels of BDNF regulation in neonatal seizures is necessary.
See this image and copyright information in PMC

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