Early Cytopathic Features in Rat Ischemia Model and Reconstruction by Neural Graft

• Published in: Experimental neurology Vol. 137; no. 2; pp. 324 - 332
• Main Authors: Onizuka, Keiichiro, Fukuda, Atsuo, Kunimatsu, Mitoshi, Kumazaki, Michiko, Sasaki, Makoto, Takaku, Akira, Nishino, Hitoo
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.1996; Elsevier
• Subjects: Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biological and medical sciences; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Brain Ischemia - surgery; Brain Tissue Transplantation; Cell Death; Disease Models, Animal; Electric Stimulation; Immunohistochemistry; Male; Medical sciences; Methamphetamine - pharmacology; Neurons - transplantation; Neurosurgery; Rats; Rats, Wistar; Skull, brain, vascular surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Animal model; Nervous system diseases; Pathophysiology; Rat; Rodentia; Homograft; Cardiovascular disease; Cerebral disorder; Functional capacity; Vascular disease; Pathology; Regeneration; Vertebrata; Mammalia; Neuron; Treatment; Ischemia; Interconnection; Surgery; Animal; Central nervous system disease; Graft; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.1996.0033

Using a silver impregnation (argyrophil III) and immunohistochemistry, acute cytopathic features after cerebral ischemia were investigated. Additionally, functional recovery and interconnection between the host and graft was also explored after neural graft. Animals were embolized in unilateral middle cerebral artery for 1 h. Argyrophil III method demonstrated “collapsed” dark neurons in the striatum, cortex, reticular thalamus, amygdala, and hypothalamus on ischemic side. These neurons exhibited characteristic shrunken somata with corkscrew-like dendrites, suggesting changes in cytoskeletal protein. In the above mentioned areas, the loss of immunoreactivity for μ-calpain proenzyme and microtubule-associated protein 2 was also detected. Neural graft into the ischemic striatum was made 2 weeks after the ischemia paradigm. The grafted striatal cells were prepared from E15 fetuses to make cell suspension marked by rhodamine-labeled latex microspheres. Methamphetamine-evoked rotations were detected after ischemia. These motor alterations were reduced gradually but significantly at 8 weeks after the graft. Interconnection between the host and grafted cells was then studied in a brain slice preparation after loading fura-2 AM. About 10% of grafted cells tested from rats that showed motor amelioration exhibited [Ca2+]iincrease to the electrical stimulation applied to the neighboring host tissue. Data indicate that, in the very early stage after ischemia, cytoskeletal damages, especially on microtubules, started and this would lead to later infarct. The graft survived in the ischemic striatum having connections with the host, and this might be partly involved in the amelioration of motor function.