Table 1.

Summary of Injury Mechanisms from Tertiary bTBI

Reference	In-vitro injury	RM	IM	IC	O	Major finding
Charles et al., 1991	Astrocyte deformation		X	X		Ca2+ signaling after stretch
Floyd et al., 2004	Astrocyte deformation		X	X		Uncoupling of IP3 signaling from Ca2+
Ellis et al., 1995; Rzigalinski et al., 1997; Rzigalinski et al., 1998; Chen et al., 2004	Astrocyte deformation		X		X	Ca2+ influx; cytoskeletal alteration;  organelle disruption
Lamb et al., 1997	Astrocyte deformation			X	X	Generation of hydroxyl and oxyradicals
Ahmed et al., 2000;  Ahmed et al., 2002	Astrocyte deformation			X	X	Decreased ATP and mitochondria  membrane potential; increase  in intracellular free [Ca2+]
Hoffman et al., 2000;  Floyd et al., 2001	Astrocyte deformation			X	X	Free radical generation; IP3
Ellis et al., 2007	Astrocyte deformation				X	Mechanical threshold for release  of S100B, neuroprotective protein
Di et al., 2000	Astrocyte deformation		X			Volume-activated ion channel changes
Floyd et al., 2005	Astrocyte deformation		X			Intracellular [Na+] increases after injury
Ostrow et al., 2000	Astrocyte deformation	X	X	X		Cytoplasmic Ca2+, IP3 increases, leading  to increased endothelin-1 production
Lea et al., 2002	Astrocyte deformation	X				mGluR5 regulates NMDAR in mild,  but not in severe stretch
Neary et al., 2003;  Neary et al., 2005;  Neary and Kang, 2006	Astrocyte deformation	X		X		Purinergic receptor activation,  signaling cascades
Zhang et al., 1996	Neuronal stretch	X				Stretch-induced relief of Mg+ blockade  of NMDAR
Geddes et al., 2003a;  Serberst et al., 2005;  Serberst et al., 2006	Neuronal stretch				X	Increases in membrane permeability  after injury
Goforth et al., 1999, 2004	Neuronal stretch	X		X		Loss of AMPAR desensitization and  potentiation of AMPA-evoked  currents after injury
Kao et al., 2004	Neuronal stretch	X		X		Potentiation of GABA currents
Tavalin et al., 1997	Neuronal stretch	X	X			NMDAR delayed depolarization;  mediated by electrogenic Na+ pump
Geddes et al., 2003b;  Lusardi et al., 2004b	Neuronal stretch		X			Changes in cytosolic Ca2+ from  NMDAR activation and mechanical pores
Chen et al., 2004	Neuronal stretch	X	X			mGluR anatogonists prevent Ca2+  depletion of stores
Arundine et al., 2003	Neuronal stretch	X	X			Stretch induces signaling cascade  through NMDAR
Lea et al., 2003	Neuronal stretch	X				Glia affects mGluR-1-mediated NMDAR  modulation in neurons
Weber et al., 2001;  Weber et al., 1999	Neuronal stretch		X	X		Intercellular Ca2+ store mediated  signaling changes
Pike et al., 2000	Neuronal stretch			X		Calpain/caspase activation follows injury
Slemmer and Weber, 2005	Repeated neuronal  stretch				X	Cumulative damage with repeated injuries
Movsesyan and Faden, 2006	In vivo controlled  cortical impact	X				mGluR2 activation is neuroprotective
Wolf et al., 2001;  Iwata et al., 2004	Axonal stretch		X			NaCh dysregulation leads to influx of Ca2+
Cargill and Thibault, 1996	Neuronal stretch  and hypoxia		X			Acute Ca2+ influx depends on rate  and severity of mechanical injury
Glass et al., 2002	Neuronal stretch  and hypoxia					Combined stretch and hypoxia resulted  in increased cell death over single  stretch or hypoxia
Engel et al., 2005	Neuronal stretch  and hypoxia					Increased cell death with combined  treatment; neuroprotective agents  not effective

RM, receptor mediated; IM, ion mediated; IC, intracellular signaling; O, other.