Adrenal medullary implants in the dopamine-denervated rat striatum. I. Acute catecholamine levels in grafts and host caudate as determined by HPLC-electrochemistry and fluorescence histochemical image analysis.
Rats with unilateral 6-hydroxydopamine-induced degeneration of the left nigrostriatal dopamine system were given intrastriatal implants of one cortex-free adrenal medulla divided into 4 pieces. Two pieces were placed in the center of the anterior part of the denervated caudate and two pieces in a more posterior position in lateral caudate. The distribution of catecholamines (CA) in grafts and host brain was studied 2, 100 and 400 min after grafting by HPLC-electrochemistry and Falck-Hillarp fluorescence histochemistry combined with computer-aided image analysis. Two minutes after implantation the chromaffin tissue grafts contained large amounts of adrenaline (A) and noradrenaline (NA) and small amounts of dopamine (DA). The chromaffin cells had a relatively normal fluorescence histochemical appearance. From the grafts, CA had spread into the surrounding host brain tissue where high levels of A and NA and low levels of DA were now found in the denervated host striatum. Fluorescence histochemistry and image analysis showed the CA to have spread 1-1.5 mm in all directions from the grafts. The CA concentrations decreased almost linearly with increasing distance from the grafts. At 100 min after implantation approximately a third of the chromaffin cells were still strongly fluorescent while the rest of the cells were very weakly fluorescent or non-fluorescent. The amounts of A, NA and DA in the host brain had decreased considerably, while the size of the fluorescent halo around the grafts had not diminished. At 400 min after grafting, only scattered cells in the chromaffin implants were strongly fluorescent and the surrounding host striatum contained low amounts of CA. It is concluded that intrastriatal adrenal medullary implants acutely release or leak large amounts of CA into surrounding host brain tissue. Taken together with results from the accompanying paper these data show that the grafts can maintain CA levels in host striatum high enough to elicit strong rotational responses during approximately 200 min.
D000313:Adrenal Medulla / Q000637:transplantation*; D000818:Animals; D002395:Catecholamines / Q000032:analysis*; D002421:Caudate Nucleus / Q000032:analysis*; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis; D004837:Epinephrine / Q000032:analysis; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D016627:Oxidopamine; D010300:Parkinson Disease / Q000628:therapy*; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D006892:Hydroxydopamines; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine