Purkinje cell damage

Figure 16-8. Section of rat brain and cerebellum zone after exposure to toxic chemicals. Note the damaged Purkinje cells and the loss of dendrites.

Finally, other factors but the onconeural antibodies may predispose an individual to neuronal damage or contribute to inflammation. We have reported lack of expression of the complement regulator protein CD59 on the surface of Purkinje cells in individuals with PCD, indicating vulnerability to the effects of complement activation [202]. Complement depositis have been found in the brain stem of a patient with paraneoplastic OM [80], Others have found absent or weak complement deposition in postmortem studies of the brain of PEM/SN patients [41, 203, 204], suggesting that... 

Finally, a relationship between intraperitoneal (i.p.) administration and the damages in Purkinje cells through intracellular calcium-binding proteins was recently reported (Franchinia et al. 2005). However, it is not easy to establish a direct relationship between mechaiusm of action and i.p. administration, since no data about YTX bioavailability is reported and the route has high variability in the doses administrated and in the effect reported (see below). 

There are not many studies addressing the potential toxicity of ethylmercury in animal models. Exposure of rats to ethylmercury results in patchy damage to the granule cells in the cerebellum while the Purkinje cells are generally spared. 

Strahlendorf, J.C., Acosta, S., and Strahlendorf, H.K., 1996. Diazoxide and cyclothiazide convert AMPA-induced dark cell degeneration of Purkinje cells to edematous damage in the cerebellar slice. Brain Res., 729, pp. 197-204. 

A single intraperitoneal administration of butylphthalide (30) (50-100 mg/kg) prolonged pentobarbital-induced sleep time in male Albino mice [287]. A similar effect was also observed after inhalation of 30 at 0.5-lmg/3L air/min [288-290]. Furthermore, in a rat chronic seizure model induced by coriaria lactone [291-295], significant damage was found in the cerebral neurons and cerebellar Purkinje cells in control animals after seizure induction, but not in rats orally pretreated with 700 mg/kg of phthalide 30. In addition, compound 30 appeared to antagonize learning and memory impairment in the same animal model. 

Disopyramide administration reduces membrane responsiveness in Purkinje fibers and ventricular muscle and reduces the action potential amplitude. Even greater depression may occur in damaged or injured myocardial cells. Action potentials are prolonged after disopyramide administration, and this results in an increase in the ERPs of His-Purkinje and ventricular muscle tissue. Unlike procainamide and quinidine, disopyramide does not produce postrepolarization refractoriness. 

---