**5.2. Carbon monoxide**

The histo-/cytotoxicity of CO is due to its high affinity to iron-containing structures such as hemoglobin and myoglobin, as well as to specific sites of the brain, including the globus pallidus and the midbrain substantia nigra, which is different from cyanide, sulfide and azide (Knight & Saukko, 2004; Oehmichen et al., 2006). CO also depresses myocardial function, resulting in severe hypotension and subsequent global cerebral ischemia and hypoxia. Bilateral necrosis of the globus pallidus and the pars reticulata of the midbrain substatia nigra are known as non-specific alterations (Oehmichen et al., 2006); however, neuronal apoptosis in the pallidum has been suggested as an early change due to CO intoxication in an animal experiment (Piantadosi et al., 1997). With respect to this, immunohistochemistry of ssDNA demonstrated high positivity as a sign of apoptosis in the pallidum of the human brain in fatal CO intoxication (Table 3) (Michiue et al., 2008; Wang et al., 2011a). Similar findings were detected in acute and delayed fire fatalities having a fatal level of blood carboxyhemoglobin (COHb) saturation, different from those with lower COHb level, as described below. These findings indicate the specific neurotoxicity of CO to the pallidum.

## **5.3. Drug abuse**

A variety of psychostimulants, narcotics and hallucinogens are involved in drug abuse, which results in brain damage and functional impairment. Among these drugs, animal experiments have shown that amphetamine and its derivatives, such as methamphetamine and ecstasy, induce apoptosis of cortical and striatal neurons, and cerebellar granular cells via various pathways (Cunha-Oliveira et al., 2008). Neuronal apoptosis has also been suggested with cocaine and opiates (Cunha-Oliveira et al., 2008). In forensic autopsy materials, immunohistochemistry also detected high neuronal ssDNA positivity as a sign of apoptosis in the cerebral cortex, pallidum and substantia nigra in fatal abuse of sedative hypnotics as well as methamphetamine, suggesting selective neuronal damage (Table 3) (Michiue et al., 2008).
