# Neonatal anesthesia-induced delay of axon pruning in hippocampus

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2020 · $67,446

## Abstract

Project Summary
Millions of human fetuses and infants are exposed every year to anesthetic drugs in doses that trigger
widespread neuroapoptosis in the developing brains of rodents and non-human primates. Alarmingly, several
clinical studies now link human infant anesthesia to cognitive deficits in later life. However, the adult mammalian
brain has orders of magnitude more neurons that survive the insult than those that are deleted and why a young
and pliable brain cannot recover from a brief anesthetic insult is not understood. A plausible hypothesis is that
the surviving neurons form dysfunctional neural circuits. Indeed, neonatal exposure to anesthetic drugs deranges
nearly every microscopic component of neural circuits, which, we hypothesize, compromises neural circuit
function, synaptic morphology, and ultimately, cognition. For Specific Aim 1, we test the hypothesis that
anesthetic drug interference with normal developmental axon pruning leads to neural circuit excitability in animals
treated with ketamine as neonates. For Specific Aim 2, we test the hypothesis that ketamine-induced deficits in
hippocampus-dependent memory and axonal pruning can be prevented through pharmacological enhancement
of BDNF signaling pathways. During the tenure of the award, the applicant will benefit from a highly-tailored
professional development curriculum that leverages the strengths of the University of Colorado, generally, and
its Department of Anesthesiology, specifically. At the conclusion of the award, the applicant will have mastery of
patch clamp electrophysiology, neurobehavioral, molecular, and morphological techniques that will help launch
his career investigating the anesthesia effects on neural circuits. The applicant’s long-term goal is to identify safe
and effective strategies that prevent anesthetic drugs from exerting deleterious effects, which will be a valuable
contribution to the health and well-being of millions of infants and children worldwide.

## Key facts

- **NIH application ID:** 9911948
- **Project number:** 1F32HD101357-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Omar Hosea Cabrera
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9911948

## Citation

> US National Institutes of Health, RePORTER application 9911948, Neonatal anesthesia-induced delay of axon pruning in hippocampus (1F32HD101357-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9911948. Licensed CC0.

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