The role of primary blast in blast-induced traumatic brain injury (bTBI) is controversial in part due to the technical difficulties of generating free-field blast conditions in the laboratory. The use of traditional shock tubes often results in artifacts, particularly of dynamic pressure, whereas the forces affecting the head are dependent on where the animal is placed relative to the tube, whether the exposure is whole-body or head-only, and on how the head is actually exposed to the insult (restrained or not). An advanced blast simulator (ABS) has been developed that enables high-fidelity simulation of free-field blastwaves, including sharply defined static and dynamic overpressure rise times, underpressures, and secondary shockwaves. Rats were exposed in head-only fashion to single-pulse blastwaves of 15 to 30 psi static overpressure. Head restraints were configured so as to eliminate concussive and minimize whiplash forces exerted on the head, as shown by kinematic analysis. No overt signs of trauma were present in the animals post-exposure. However, significant changes in brain 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) and neurofilament heavy chain levels were evident by 7 days. In contrast to most studies of primary blast-induced TBI (PbTBI), no elevation of glial fibrillary acidic protein (GFAP) levels was noted when head movement was minimized. The ABS described in this article enables the generation of shockwaves highly representative of free-field blast. The use of this technology, in concert with head-only exposure, minimized head movement, and the kinematic analysis of the forces exerted on the head provide convincing evidence that primary blast directly causes changes in brain function and that GFAP may not be an appropriate biomarker of PbTBI.

1 ATP receptors of the P2X class have previously been identi®ed on autonomic nerve endings and on a limited population of CNS neurons. 2 In the present study P2X receptors on mammalian cortical synaptosomes have been identi®ed by a variety of functional and biochemical studies. In choline bu er ATP analogues caused concentration/time dependent Ca 2+ in¯ux. Relative to the e ects caused by ATP, benzoylbenzoyl ATP (BzATP) was about seven times more active than ATP while 2-me-S-ATP and ATPgS were much less active. a,b-me-ATP and b,g-me-ATP were virtually inactive. In sucrose bu er, relative to choline bu er, the activity of BzATP was more than doubled while activity in sodium bu er was reduced. Moreover, the P2X antagonists PPADS or Brilliant Blue G both signi®cantly attenuated in¯ux. These observations suggest the presence of P2X receptors on synaptosomes which subserve Ca 2+ in¯ux. This activity pro®le of the ATP analogues and the response to blocking agents are characteristic of responses of P2X 7 receptors. 3 In¯ux was una ected by the VSCC inhibitors o-CTx-MVIIC and (7) 202 ± 791, indicating that ATP induced Ca 2+ in¯ux occurred primarily through P2X receptors. 4 P2X 7 receptor protein was identi®ed by Western blotting and immunohistochemical staining. Puri®ed preparations were devoid of signi®cant concentrations of GFAP or the microglial marker OX-42 but contained greatly enriched amounts of syntaxin and SNAP 25. 5 The various pharmacological and biochemical studies were all consistent with the presence of functional P2X 7 receptors.

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