Damage to the olfactory nerves is thought to result in anosmia (loss of olfactory function) by preventing signals from odor receptor cells from reaching the brain. At the present time little hope is offered to those with impaired olfactory function. This project will combine molecular techniques with a nerve regeneration model to investigate the capacity of olfactory neurons to regenerate, replace, and repair damaged neurons in the central nervous system. Genetic markers introduced into a strain of transgenic mice will be used to trace regenerating olfactory nerves as they grow back to their target sites in the olfactory bulb. Experiments will determine if the regenerating nerve fibers can restore sensory maps in olfactory brain regions. Age related changes in sensory maps will also be investigated. Immunocytochemical methods will be used to determine the time course and location of new synapse formation during recovery from nerve transection. Behavioral experiments will determine the amount of reconnection needed to restore odor mediated behavior and if increasing odor exposure (odor therapy) helps to improve the time course of recovery. Results from this study could have important clinical implications for rehabilitation and recovery of function following brain injury. Findings could provide the foundation for future treatment strategies to help improve or restore function in individuals with anosmia and other brain related injuries.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000165-19
Application #
6634413
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Davis, Barry
Project Start
1980-12-01
Project End
2006-03-31
Budget Start
2003-07-01
Budget End
2006-03-31
Support Year
19
Fiscal Year
2003
Total Cost
$230,913
Indirect Cost
Name
Virginia Commonwealth University
Department
Physiology
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Reiter, Evan R; Costanzo, Richard M (2012) Chemosensory Impairment after Traumatic Brain Injury: Assessment and Management. Int Neurotrauma Lett 23:
Costanzo, Richard M; Yagi, Sayaka (2011) Olfactory epithelial transplantation: possible mechanism for restoration of smell. Curr Opin Otolaryngol Head Neck Surg 19:54-7
Nadkarni, P P; Costanzo, R M; Sakagami, M (2011) Pulmonary delivery of peptide YY for food intake suppression and reduced body weight gain in rats. Diabetes Obes Metab 13:408-17
Bakos, Stephen R; Costanzo, Richard M (2011) Matrix metalloproteinase-9 is associated with acute inflammation after olfactory injury. Neuroreport 22:539-43
Bakos, Stephen R; Schwob, James E; Costanzo, Richard M (2010) Matrix metalloproteinase-9 and -2 expression in the olfactory bulb following methyl bromide gas exposure. Chem Senses 35:655-61
Costanzo, Richard M; Kobayashi, Masayoshi (2010) Age-related changes in p2 odorant receptor mapping in the olfactory bulb. Chem Senses 35:417-26
Kobayashi, Masayoshi; Costanzo, Richard M (2009) Olfactory nerve recovery following mild and severe injury and the efficacy of dexamethasone treatment. Chem Senses 34:573-80
Yagi, Sayaka; Costanzo, Richard M (2009) Grafting the olfactory epithelium to the olfactory bulb. Am J Rhinol Allergy 23:239-43
Costanzo, Richard M; Perrino, Lisa A (2008) Peak in matrix metaloproteinases-2 levels observed during recovery from olfactory nerve injury. Neuroreport 19:327-31
Kobayashi, Masayoshi; Reiter, Evan R; DiNardo, Laurence J et al. (2007) A new clinical olfactory function test: cross-cultural influence. Arch Otolaryngol Head Neck Surg 133:331-6

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