Article abstract-The recent formulation of guidelines for the management of concussion in sports adopted by the American Academy of Neurology specifically calls for the development of a standardized, systematic sideline evaluation for the immediate assessment of concussion in athletes. The present study involved the preliminary investigation of the feasibility and clinical validity of a standardized version of a brief sideline examination complied in accordance with these guidelines. This examination, intended for use by athletic trainers, was administered by three trainers to 141 nonconcussed high school football players at three separate schools. All players suspected of suffering a concussion (N = 6) during the fall 1995 season were also tested immediately following their injury. The examination was easily administered and scored. The concussed players as a group scored significantly below the nonconcussed controls and below their own baseline (pre-injury) performance, despite their all having been considered by the trainers to have suffered mild, grade 1 concussions. Although preliminary, these data suggest that a standardized sideline examination of this type can be useful in detecting concussion and determining fitness to return to play.

Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

Caenorhabditis elegans TOM-1 is orthologous to vertebrate tomosyn, a cytosolic syntaxin-binding protein implicated in the modulation of both constitutive and regulated exocytosis. To investigate how TOM-1 regulates exocytosis of synaptic vesicles in vivo, we analyzed C. elegans tom-1 mutants. Our electrophysiological analysis indicates that evoked postsynaptic responses at tom-1 mutant synapses are prolonged leading to a two-fold increase in total charge transfer. The enhanced response in tom-1 mutants is not associated with any detectable changes in postsynaptic response kinetics, neuronal outgrowth, or synaptogenesis. However, at the ultrastructural level, we observe a concomitant increase in the number of plasma membrane-contacting vesicles in tom-1 mutant synapses, a phenotype reversed by neuronal expression of TOM-1. Priming defective unc-13 mutants show a dramatic reduction in plasma membrane-contacting vesicles, suggesting these vesicles largely represent the primed vesicle pool at the C. elegans neuromuscular junction. Consistent with this conclusion, hyperosmotic responses in tom-1 mutants are enhanced, indicating the primed vesicle pool is enhanced. Furthermore, the synaptic defects of unc-13 mutants are partially suppressed in tom-1 unc-13 double mutants. These data indicate that in the intact nervous system, TOM-1 negatively regulates synaptic vesicle priming.

Leukocyte-common antigen related (LAR)-like phosphatase receptors are conserved cell adhesion molecules that function in multiple developmental processes. TheCaenorhabditis elegans ptp-3gene encodes two LAR family isoforms that differ in the extracellular domain. We show here that the long isoform, PTP-3A, localizes specifically at synapses and that the short isoform, PTP-3B, is extrasynaptic. Mutations inptp-3cause defects in axon guidance that can be rescued by PTP-3B but not by PTP-3A. Mutations that specifically affectptp-3Ado not affect axon guidance but instead cause alterations in synapse morphology. Genetic double-mutant analysis is consistent withptp-3Aacting with the extracellular matrix component nidogen,nid-1, and the intracellular adaptor α-liprin,syd-2.nid-1andsyd-2are required for the recruitment and stability of PTP-3A at synapses, and mutations inptp-3ornid-1result in aberrant localization of SYD-2. Overexpression of PTP-3A is able to bypass the requirement fornid-1for the localization of SYD-2 and RIM. We propose that PTP-3A acts as a molecular link between the extracellular matrix and α-liprin during synaptogenesis.