Fiber Sprouting Research Articles

Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting.

We used the pilocarpine model of chronic spontaneous recurrent seizures to evaluate the time course of supragranular dentate sprouting and to assess the relation between several changes that occur in epileptic tissue with different behavioral manifestations of this experimental model of temporal lobe epilepsy. Pilocarpine-induced status epilepticus (SE) invariably led to cell loss in the hilus of the dentate gyrus (DG) and to spontaneous recurrent seizures. Cell loss was often also noted in the DG and in hippocampal subfields CA1 and CA3. The seizures began to appear at a mean of 15 days after SE induction (silent period), recurred at variable frequencies for each animal, and lasted for as long as the animals were allowed to survive (325 days). The granule cell layer of the DG was dispersed in epileptic animals, and neo-Timm stains showed supra- and intragranular mossy fiber sprouting. Supragranular mossy fiber sprouting and dentate granule cell dispersion began to appear early after SE (as early as 4 and 9 days, respectively) and reached a plateau by 100 days. Animals with a greater degree of cell loss in hippocampal field CA3 showed later onset of chronic epilepsy (r = 0.83, p < 0.0005), suggesting that CA3 represents one of the routes for seizure spread. These results demonstrate that the pilocarpine model of chronic seizures replicates several of the features of human temporal lobe epilepsy (hippocampal cell loss, supra- and intragranular mossy fiber sprouting, dentate granule cell dispersion, spontaneous recurrent seizures) and that it may be a useful model for studying this human condition. The results also suggest that even though a certain amount of cell loss in specific areas may be essential for chronic seizures to occur, excessive cell loss may hinder epileptogenesis.

Seizure Stage, Persistence of Kindled Epileptogenesis, and Mossy Fiber Sprouting

Seizure Stage, Persistence of Kindled Epileptogenesis, and Mossy Fiber Sprouting

Regenerating sprouts of axotomized cat muscle afferents express characteristic firing patterns to mechanical stimulation

1. In cats, we studied the physiological properties of regenerating sprouts of muscle afferent fibers and compared them with sprouts from cutaneous afferent fibers. 2. Muscle nerves to the triceps surae and cutaneous sural nerves were axotomized in the popliteal fossa, and the proximal ends were inserted into nerve cuffs. Six days later, we recorded action potentials from single Groups I and II muscle and mostly Group II cutaneous afferents driven by mechanostimulation of the cuff. 3. Most muscle afferent sprouts (91%) had a regular slowly adapting discharge in response to sustained mechanical displacement of the cuff, particularly to sustained stretch stimuli, whereas most cutaneous afferents (92%) did not. Muscle afferents were more likely to have a spontaneous discharge and afterdischarge. 4. Group II muscle afferent sprouts had lower stretch thresholds and a higher incidence of spontaneous discharge compared with Group I fiber sprouts, whereas Group I fibers had a higher incidence of high-frequency afterdischarge to mechanical stimuli. 5. We conclude that, 6 days after axotomy, regenerating sprouts of muscle afferents, particularly Group II afferents, have become mechanosensitive in the absence of a receptor target and exhibit physiological properties similar to those found when innervating their native muscle but significantly different from sprouts of cutaneous afferents. Expression of these native muscle afferent firing patterns after the inappropriate reinnervation of hairy skin may be due to inherent properties of the muscle afferent fiber.

Electrotonic coupling between granule cells of rat dentate gyrus: physiological and anatomical evidence.

Electrotonic coupling between granule cells of rat dentate gyrus: physiological and anatomical evidence.