Available online at www.sciencedirect.com Neuroscience Letters 434 (2008) 247–252 Up-regulation of reactivity and survival genes in astrocytes after exposure to short duration overpressure Pamela J. VandeVord a,b,∗ , Lai Yee Leung a , Warren Hardy a , Matthew Mason a , King H. Yang a , Albert I. King a a Department of Biomedical Engineering, Wayne State University, 818 West Hancock, Detroit, MI 48202, USA b John D. Dingell VA Medical Center, Research and Development Service, Detroit, MI 48201, USA Received 26 October 2007; received in revised form 21 December 2007; accepted 9 January 2008 Abstract Gurdjian et al. proposed decades ago that pressure gradients played a major factor in neuronal injury due to impact. In the late 1950s, their experiments on concussion demonstrated that the principal factor in the production of concussion in animals was the sudden increase of intracranial pressure accompanying head injury. They reported the increase in pressure severity correlated with an increase in ‘altered cells’ resulting in animal death. More recently, Hardy et al. (2006) demonstrated the presence of transient pressure pulses with impact conditions. These studies indicate that short duration overpressure should be further examined as a mechanism of traumatic brain injury (TBI). In the present study, we designed and fabricated a barochamber that simulated overpressure noted in various head injury studies. We tested the effect of overpressure on astrocytes. Expressions of apoptotic, reactivity and survival genes were examined at 24, 48 and 72 h post-overpressure exposure. At 24 h, we found elevated levels of reactivity and survival gene expression. By 48h, a decreased expression of apoptotic genes was demonstrated. This study reinforces the hypothesis that transient pressure acts to instigate the cellular response displayed following TBI. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Astrocytes; Overpressure; Reactivity; Survival; Apoptosis; Traumatic brain injury The mechanisms underlying cell death following traumatic brain injury (TBI) are not fully understood. Studies in impact biome- chanics have demonstrated a number of brain injury mechanisms [14]. These mechanisms include positive pressures at the impact site, negative pressure at the site opposite of impact, pressure gradients and rotational effects causing strain. Gurdjian et al. proposed several decades ago that pressure gradients played a major factor in neuronal injury due to impact [10]. Their ini- tial experiments on concussions demonstrated that the principal factor in the production of concussion was the sudden increase in intracranial pressure that accompanied head injury [2]. The increase in pressure pulse severity was found to be correlated with an increase in ‘altered cells’ in the brain. More recently, Hardy et al. demonstrated the presences of transient pressure pulses with impact conditions [11]. Coup pressures measured within a pressurized cadaver head after impact ranged from 34 to 160 kPa, and the contrecoup pressures ranged from -2 to ∗ Corresponding author. Tel.: +1 313 577 3852; fax: +1 313 577 8333. E-mail address: pvord@wayne.edu (P.J. VandeVord). -48 kPa. Collectively, these studies indicate that pressure should be further examined as a mechanism of TBI. Thus, we designed and fabricated a barochamber that simulates overpressure con- ditions noted in head injury studies to examine the cellular response to overpressure. TBI is known to initiate a complex sequence of destructive and neuroprotective cellular responses. As a consequence of the initial mechanical impact to the head, it is known that cerebral metabolism, blood flow and ion homeostasis become altered for a period of hours to months [25]. During secondary injury, high levels of glutamate, calcium and cytokines are released, con- tributing to additional tissue damage [16]. Beside this destructive process, neuroprotective events in repair and regeneration also take place [26]. The balance between these harmful and pro- tective factors plays an important role in cell survival. One hypothesis is that glial cells provide positive and negative fac- tors that determine neuronal death. Astrocytes are crucial for neuronal metabolic, antioxidant, and trophic support, as well as normal synaptic function. The relationship between neurons and astrocytes appears to play an important role for the repair of the injured central nervous system (CNS). Katano et al. reported that 0304-3940/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2008.01.056