Asphyxial death has been a problem for forensic investigations due to the absence of a validated biomarker for the diagnosis of this event. Recently, research on brain affection by asphyxia raised hopes on the possible use of CNS markers for asphyxia. The cytoskeletal proteins seem to be attractive targets as they are vulnerable to hypoxia and can be affected in asphyxial deaths. Tau, an important cytoskeletal protein, showed affection in many neurodegenerative disorders and recently in some acute incidences like trauma and brain ischemia. In this report we show the affection of the normal pattern of tau and pathological aggregates of tau in the case of brain hypoxia. This may give new clues to asphyxial death investigations.
Aging related reduction in cerebral blood flow (CBF) has been linked with neurodegenerative disorders including Alzheimer's disease and dementia. Experimentally, a condition of chronic cerebral hypoperfusion due to reduced CBF can be induced by permanent bilateral occlusion of common carotid arteries (2-vessel occlusion, 2VO) in rats. Since oxidative stress, leading to neuronal apoptosis and death, is one of the mechanisms, which is thought to play a significant role in chronic degenerative neurological disorders, the present study was planned to assess the ROS status by measuring the levels of anti-oxidant enzymes that might occur during chronic cerebral hypoperfusion. Antioxidant enzymes namely glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase were measured in the brain tissue at eight weeks of 2VO induction in rats. Results show significantly elevated levels of GPx, SOD, and catalase enzymes as compared with the control group. It is possible that compensatory rise in antioxidant enzymes occurs in response to increased oxidative stress following ischemic insult.
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD. The PD model was developed in C57BL/6 mice using intraperitoneal rotenone administration for 60 consecutive days. MSCs were isolated from the mononuclear cell fraction of pooled bone marrow from C57BL/6 mice and incubated with micrometer-sized iron oxide (MPIO) particles. For IN administration, we used a 20 µl of 5×10(5) cell suspension. Neurobehavioral assessment of the mice was performed, and after sacrifice, brain sections were stained with Prussian blue to detect the MPIO-labeled MSCs. In addition, immunohistochemical evaluation was conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurobehavioral assessment revealed progressive deterioration in the locomotor functions of the rotenone group, which was improved following MSC administration. Histopathological evaluation of brain sections in the rotenone+MSC group revealed successful delivery of MSCs, evidenced by positive Prussian blue staining. Furthermore, rotenone treatment led to significant decrease in dopaminergic neuron number in SNpc, as well as similar decrease in the corpus striatum fiber density. By contrast, in animals receiving IN administration of MSCs, the degeneration caused by rotenone treatment was significantly counteracted. In conclusion, the present study validated that IN delivery of MSCs may be a potential safe, easy and cheap alternative route for stem cell treatment in neurodegenerative disorders.