Oculomotor nerve regeneration in rats. Functional, histological, and neuroanatomical studies

To study oculomotor nerve regeneration in rats, the oculomotor nerve was approached microsurgically and was sectioned at the base of the skull. The nerve stumps were reapproximated and affixed with a plasma clot in Group I animals and were separated by a gap in Group II animals. Visceral eye motility was evaluated weekly between 1 day and 40 weeks after surgery by recording the pupillary diameter under standardized photic stimulation. Somatic eye motility was assessed after 26 weeks by measuring the ocular displacement evoked by vestibular stimulation in the horizontal and vertical planes. Nerve regeneration was documented histologically and morphometrically at 8, 16, and 40 weeks after section. The selectivity of axonal regeneration to the extraocular muscles was investigated after 26 weeks by mapping (with injection of retrograde horseradish peroxidase) the motoneurons that supplied each reinnervated muscle. Between 6 and 20 weeks after section, the pupil diameter showed a progressive reduction in Group I rats, and no changes were observed in Group II rats. Compared with normal rats, the amplitude of horizontal and vertical ocular displacements was decreased, respectively, by 30% and 45% in Group I and by 65% and 80% in Group II. In Group I rats, the vestibular stimulation in the horizontal plane evoked anomalous eye movements with vertical components. On histological examination, regenerated nerves showed a progressive increase of axonal diameter and myelin-sheath thickness. Reinnervated muscles were associated with a less specific, bilateral representation in the midbrain compared with normal muscles, which have unilateral representation. The changes of the somatotopic organization were interpreted as being the result of the misdirected regrowth of axons in the postlesional nerve stump and of the collateral sprouting in the midbrain.