Motor, cytoarchitectural and biochemical assessment of pharmacological neuroprotection against CNS damage induced by neonatal exposure to ionizing radiation.
Exposure of neonatal rats to a 5 Gy single dose of X-irradiation induces permanent abnormalities in cerebellar cortex cytoarchitecture and neurochemistry and motor function. This rodent model constitutes an useful tool to evaluate morphological, neurochemical and motor changes induced by ionizing radiation and the possible restorative effects of potential or clearly established neuroprotective drugs. After selection and administration of a neuroprotective agent to neonatally irradiated rats, quantitative evaluations of motor behavior (gait), cerebellar cortex cytoarchitecture and cerebellar monoamine levels are performed. Data are compared to those of both saline-injected, X-irradiated, and saline-injected, sham-irradiated controls. Evaluation of data from the different experimental groups is performed at postnatal days 30 and 90. After this postnatal interval, radiation-induced damage of cerebellar function in nonprotected rodents is considered to be permanent. The longitudinal evaluation of various parameters in the different experimental groups through a multidisciplinary approach, allows determination of the variables that are more sensitive to X-irradiation-induced damage and/or neuroprotective agent-induced restoration. Given the well-known correspondence in cerebellar developmental stages between rodents and humans, this model and related studies bring health-related implications, considering the accidental or therapeutic exposure of developing human beings to ionizing radiation.
Guelman
L R
LR
1a Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, UBA, Paraguay 2155, piso 15, 1121 Buenos Aires, Argentina. lguelman@fmed.uba.ar
Zorrilla Zubilete
M A
MA
Ríos
H
H
Di Toro
C G
CG
Dopico
A M
AM
Zieher
L M
LM
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D005260:Female; D005684:Gait / Q000187:drug effects; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence
D007202:Indicators and Reagents; D018696:Neuroprotective Agents; D011837:Radiation-Protective Agents; D009638:Norepinephrine