The effect of lumbar spinal nerve (SN) transection on estimates of neuron number was investigated in the dorsal root ganglia (DRGs) of juvenile bullfrogs (Rana catesbeiana). SN8 and SN10 were transected on one side, and SN9 was left intact. Two weeks after nerve injury, estimates of neuron number in DRG8 and DRG10 on both the operated and unoperated sides were more than twice the estimates obtained from control animals. Neuron number in the uninjured DRG9 was also elevated relative to that of control animals. Eight weeks after axotomy, differences in neuron number were less apparent. The mean cross-sectional area of DRG neurons was reduced 2 weeks after nerve injury in all DRGs. The decrease in mean area was the result of the addition of neurons to the smallest size classes. These data are discussed in the context of previous results showing that neurons are added as juvenile frogs grow to adult size (St. Wecker and Farel [1994] J. Comp. Neurol. 342:430-438). This addition results from the maturation of a population of incompletely differentiated neurons (Meeker and Farel [1997] J. Comp. Neurol. 389:569-576). The present results suggest that axotomy precipitates differentiation of these incompletely differentiated neurons, perhaps as a compensatory response to nerve injury.
The effect of lumbar spinal nerve (SN) transection on estimates of neuron number was investigated in the dorsal root ganglia (DRGs) of juvenile bullfrogs (Rana catesbeiana). SN8 and SN10 were transected on one side, and SN9 was left intact. Two weeks after nerve injury, estimates of neuron number in DRG8 and DRG10 on both the operated and unoperated sides were more than twice the estimates obtained from control animals. Neuron number in the uninjured DRG9 was also elevated relative to that of control animals. Eight weeks after axotomy, differences in neuron number were less apparent. The mean cross‐sectional area of DRG neurons was reduced 2 weeks after nerve injury in all DRGs. The decrease in mean area was the result of the addition of neurons to the smallest size classes. These data are discussed in the context of previous results showing that neurons are added as juvenile frogs grow to adult size (St. Wecker and Farel [1994] J. Comp. Neurol. 342:430–438). This addition results from the maturation of a population of incompletely differentiated neurons (Meeker and Farel [1997] J. Comp. Neurol. 389:569–576). The present results suggest that axotomy precipitates differentiation of these incompletely differentiated neurons, perhaps as a compensatory response to nerve injury. J. Comp. Neurol. 410:171–177, 1999. © 1999 Wiley‐Liss, Inc.
Ocular barriers to drug transport make delivery of effective doses to posterior targets exceptionally difficult. Animal models have commonly been used to evaluate drug distribution and penetrability, but translational tools to determine human dosing are lacking. Here we present a framework for modeling interspecies variation by simulating oxygen distribution in the posterior eye, from outer vitreous to the sclera. Posterior eye models of mouse, rabbit, and human are presented with modifications based solely on species-dependent anatomical and physiological differences. The model includes tissue and vascular contributions to transport. In addition to oxygen, nitric oxide and its impact on oxygen metabolism is simulated. Depth-dependent retinal oxygen partial pressure profiles are in good agreement with experimental data for all three species. The model can be further extended to evaluate the variations of retinal oxygenation in response to various drugs, formulations, administration protocols, and treatment plans. Further, this framework of ocular physiologically based pharmacokinetic/pharmacodynamic models could support animal to human translation, a critical step in the drug development process.
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