**7.2. Hypothermia (Cold exposure)**

264 Apoptosis and Medicine

positivity in the pallidum due to CO intoxication; 2) neuronal loss in prolonged death; 3) overall low glial bFGF and GFAP immunopositivities with high neuronal ssDNA immunopositivity in prolonged death due to CO intoxication (Table 3) (Wang et al., 2011a). These findings suggest neuronal loss and progressive apoptosis without glial responses after CO intoxication; the brain sustained serious damage involving the loss of self-

**Figure 2.** Immunohistochemistry of single-stranded DNA (ssDNA), basic fibroblast growth factor (bFGF) and glial fibrillary acidic protein (GFAP) in the parietal cortex of prolonged fire death cases: 1) a case of fatal burns and low blood cardoxyhemoglobin (COHb) saturation (72 h survival), showing low ssDNA (a), and high bFGF (b) and GFAP (c) positivity; 2) a case of a fatal level of blood COHb saturation (48 h survival), showing high ssDNA (d), and low bFGF (e) and GFAP (f) positivity

In forensic practice, the diagnosis of death due to extreme environmental temperatures involving hypothermia (cold exposure) and hyperthermia (heat stroke) is often difficult because of poor or nonspecific gross and microscopic findings, although hypothermia may present with typical pathologies, including frost erythema and hemorrhagic gastric erosions (Wischnewski spots) (Green et al., 2001; Nixdorf-Miller et al., 2006; Schuliar et al., 2001; Turk, 2010). Besides diagnosis by exclusion, histology, immunohistochemistry, biochemistry and molecular biology can be used for detailed investigation of functional deaths (Madea &

**7. Extreme ambient temperature** 

**7.1. General considerations** 

protective capacity in CO intoxication, thus causing delayed death.

When the human body cannot compensate for heat loss in an extremely cold environment, the body temperature decreases progressively, resulting in cerebral and cardiorespiratory dysfunction, and finally fatal arrhythmia and asystole. Metabolic deterioration involves dehydration, acidosis, azotemia and enhanced fat metabolism with ketonemia/ketouria, but myocardial and brain tissue damage are usually mild (Maeda et al., 2011).

In immunohistochemcal investigation of the brain, hypothermia cases showed higher glial bFGF immunopositivity in the cerebral cortex and white matter, and higher S100β immunopositivity in the cerebral cortex with a lower CSF S100β concentration, without glial or neuronal loss (Fig. 3 and Table 3) (Wang et al., 2012a). The up-regulation of glial bFGF and S100β in the cerebral cortex suggests the self-protective responses of the brain and possible neurotrophic properties, respectively (Gomide & Chadi, 1999). Furthermore, since bFGF may be involved in the anti-apoptotic pathways (Ay et al., 2001; Tamatani et al., 1998), high glial bFGF immunopositivity accompanied by low neuronal ssDNA expression in hypothermia cases can indicate the activation of endogenous bFGF as an anti-apoptosis factor in the brain, which is similar to previous findings in prolonged fire fatality due to burns (Wang et al., 2011a). As above, the brain may retain self-protective response capacity without marked glial or neuronal damage in fatal hypothermia. The mechanism of death may mainly involve cardiac dysfunction, including ventricular fibrillation or asystole, resulting from myocardial ischemia, hypoxia, electrolyte abnormalities and elevated catecholamine levels (Turk, 2010), although there have been few postmortem investigations (Ishikawa et al., 2010; Wang et al., 2011b). To summarize, fatal hypothermia cases showed neuroprotective glial responses without marked neuronal or glial damage, which can serve as a condition for possible recovery and survival by means of adequate resuscitation and life-supporting measures.
