Vimentin and p53 immunoreactivity in cases of traumatic brain injury

Traumatic brain injury (TBI) is one of the main causes of death in Trauma Pathology, especially among the youngest victims. The traumas that can provoke TBI are vary, first of all motor vehicle accidents, but also fall-from-height, sport accidents, etc. [1]. TBI could be described as the damage of the brain caused by the different kind of forces applied to the head [2]. Indeed, a lesion to the cerebral tissue could derived both from a direct head trauma or an indirect projection of high kinetic forces applied to the body, as it often happens in vehicle crashes [3]. Regardless of the cause, TBI is characterized by altered brain functions and/or anatomical alterations. Considering the Forensic Pathology point-of-view, TBI has always represented an issue. The first question the Pathologist should be focused on is if the brain lesions are the cause of death. Once evaluated the causality relationship between the damage to the brain tissue and the death, the second most important question is how long has been past from the TBI and the death? Understanding if there is the victim has survived, and how long it was, could be fundamental for the Judicial interpretation of a case. The immediate effects of a head trauma are called primary brain injuries (PBI). They can be focal or diffuse, according to the localization of the damage. Even if there is not a unique relationship between the type of trauma and the type of brain damage, usually low energy traumas cause focal lesions, while mild and severe head traumas cause both diffuse and focal lesions [4]. Example of focal lesions are brain contusion, haemorrhages (intracerebral, subdural or extradural), necrotic area due to reduced blood supply. Diffuse brain injury or diffuse axonal injury (DAI) involves the whole brain tissue and is the consequence of non-contact forces [5,6]. In such cases, axons are rapidly stretched, and this causes a damage of their cytoskeleton, impairing the axoplasmic transport. The swelling of the tissue that occurs soon after a stretch-trauma further aggravates axonal damage. Secondary brain injuries (SBI) could be defined as the delayed progression of PBI. Several biochemical and molecular mechanisms of damage have been described to explain SBI. Apoptosis has a main role in SBI. Beer et colleagues has demonstrated that p18, the active caspase-3 subunit, is increased in neurons, astrocytes, and oligodendrocytes of injured brain tissue from 6 to 72 hours after the trauma in rats [7]. Accordingly, Franz et al. 2002 found that Bid cleavage is enhanced from 6 hours to 7 days after TBI in rats [8]. Bid is a pro-apoptotic protein that belongs to the Bcl-2 family 2 [9]. Larner et al. 2005 have investigated the expression of Caspase 7 after a TBI in a rat model [10]. They chose caspase 7 because it is usually not present in brain tissues. They used a semiquantitative real-time polymerase chain reaction (PCR) to evaluate the caspase 7 mRNA levels, and they found they were enhanced in TBI. The peak of caspase 7 expression was obtained with different timing depending on the cerebral area: in the traumatized cortex the peak was at the fifth day after the trauma, in the hippocampus between six and 24 hours. Several studies have been conducted to evaluate the role and timing of production of apoptotic proteins after a TBI. However, most of them are based on animal models. Considering the previous knowledge on this field, our research group focused on the identification of molecules that could be used as markers of TBI with diagnostic and timing purposes. This could be useful in Judicial cases, when it is fundamental to provide solid scientific evidence to corroborate the interpretation of the events. In our previous research, we demonstrated that the expression of FOXO3a, a pro-apoptotic transcription factor, is enhanced in TBI. Furthermore, the FOXO3a immunoreaction was progressively more intense with increasing the survival time [11]. The current study is aimed to evaluate the possible role as TBI markers of vimentin and p53.