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Neuropathologic changes in suckling and weanling rats with pyrithiamine-induced thiamine deficiency
Insights
Thiamine deficiency in developing rats causes brain damage, particularly in the cerebellum, after weaning. Early pyrithiamine injections lead to neuronal swelling and hemorrhages, impacting brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Thiamine (vitamin B1) is crucial for neuronal function and brain development.
- Nutritional deficiencies during gestation and lactation can profoundly affect offspring neurodevelopment.
- Pyrithiamine is a thiamine antagonist used experimentally to induce thiamine deficiency.
Purpose of the Study:
- To investigate the neuropathologic effects of induced thiamine deficiency on developing Wistar rats.
- To characterize the timing and specific brain regions affected by pyrithiamine administration in the offspring of thiamine-deficient dams.
Main Methods:
- Pregnant and nursing Wistar rats were fed a thiamine-deficient diet.
- Offspring were administered daily injections of pyrithiamine.
- Pathologic lesions in the suckling rats were examined at various developmental stages.
Main Results:
- No significant pathologic changes were observed before 22 days of age, except for scattered petechial hemorrhages.
- After 22 days of age, acute neuropathologic changes were evident, with the vestibular nuclei, inferior olivary nuclei, and mammillary body being most severely affected.
- Initial cellular changes included post-synaptic dendrite swelling and periaxonal space distension, followed by hemorrhages and astrocytic swelling.
Conclusions:
- Pyrithiamine-induced thiamine deficiency in developing rats causes significant neuropathology, primarily after the completion of major cerebellar morphogenesis.
- The observed neuronal swelling and hemorrhages suggest a disruption of neuronal membrane electrolyte permeability and subsequent effects on brain vascular permeability.
- These findings highlight the critical role of thiamine during specific neurodevelopmental windows and the potential for nutritional insults to cause lasting brain damage.
Abstract:
Pregnant and nursing Wistar rats were fed a thiamine-deficient diet, and their offspring were injected daily with pyrithiamine. The pathologic lesions in the suckling rats were examined at different times of development. There were distinct changes at 22 days of age, by which time the rats are weaned, and the morphogenesis of the cerebellum is almost completed. Before 22 days of age, there were no pathologic changes except for scattered petechial hemorrhages in the brain. After 22 days of age, acute pathologic changes were observed, in decreasing order of severity, in the vestibular nuclei, inferior olivary nuclei, mammillary body, periventricular gray matter, thalamus, and quadrigeminal plates. The initial changes were swelling of post-synaptic dendrites and distension of the periaxonal space of myelinated axons in the parenchyma and ring-shaped hemorrhages in the perivascular space. Pyrithiamine injections into the offspring of rats fed a thiamine-deficient diet probably induce disturbance of the electrolyte permeability of the neuronal excitable membrane, resulting in swelling of this element. These changes were followed by the filtration of erythrocytes and plasma into the parenchyma and astrocytic swelling, which may be a secondary effect of neuronal changes on the brain vascular permeability.