A role for insulin-like growth factor-1 in hippocampal plasticity following traumatic brain injury

Hannah C. Williams, Shaun W. Carlson, Kathryn E. Saatman

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Scopus citations

Abstract

Traumatic brain injury (TBI) initiates a constellation of secondary injury cascades, leading to neuronal damage and dysfunction that is often beyond the scope of endogenous repair mechanisms. Cognitive deficits are among the most persistent morbidities resulting from TBI, necessitating a greater understanding of mechanisms of posttraumatic hippocampal damage and neuroplasticity and identification of therapies that improve recovery by enhancing repair pathways. Focusing here on hippocampal neuropathology associated with contusion-type TBIs, the impact of brain trauma on synaptic structure and function and the process of adult neurogenesis is discussed, reviewing initial patterns of damage as well as evidence for spontaneous recovery. A case is made that insulin-like growth factor-1 (IGF-1), a growth-promoting peptide synthesized in both the brain and the periphery, is well suited to augment neuroplasticity in the injured brain. Essential during brain development, multiple lines of evidence delineate roles in the adult brain for IGF-1 in the maintenance of synapses, regulation of neurotransmission, and modulation of forms of synaptic plasticity such as long-term potentiation. Further, IGF-1 enhances adult hippocampal neurogenesis though effects on proliferation and neuronal differentiation of neural progenitor cells and on dendritic growth of newly born neurons. Post-injury administration of IGF-1 has been effective in rodent models of TBI in improving learning and memory, attenuating death of mature hippocampal neurons and promoting neurogenesis, providing critical proof-of-concept data. More studies are needed to explore the effects of IGF-1-based therapies on synaptogenesis and synaptic plasticity following TBI and to optimize strategies in order to stimulate only appropriate, functional neuroplasticity.

Original languageEnglish
Title of host publicationHormones, Regulators and Hippocampus
EditorsGerald Litwack
Pages423-455
Number of pages33
DOIs
StatePublished - Jan 2022

Publication series

NameVitamins and Hormones
Volume118
ISSN (Print)0083-6729

Bibliographical note

Funding Information:
This work was supported by grants from the National Institutes of Health National Institute of Neurological Disorder and Stroke (NS092552 and NS111099) and National Institute of General Medical Sciences T32 Predoctoral Fellowship Program (GM118292) and the Kentucky Spinal Cord and Head Injury Research Trust (KSCHIRT 19-5A).

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • Closed head injury
  • Controlled cortical impact
  • Hippocampus
  • IGF-1
  • Neurogenesis
  • Synapse
  • Synaptic function

ASJC Scopus subject areas

  • Physiology
  • Endocrinology

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