Perinatal hypoxia is still one of the greatest threats to the
newborn child, even in developed countries. However, there is
a lack of works which summarize up-to-date information about
that huge topic. Our review covers a broader spectrum of recent
results from studies on mechanisms leading to hypoxia-induced
injury. It also resumes possible primary causes and observed
behavioral outcomes of perinatal hypoxia. In this review, we
recognize two types of hypoxia, according to the localization of
its primary cause: environmental and placental. Later we analyze
possible pathways of prenatal hypoxia-induced injury including
gene expression changes, glutaminergic excitatory damage (and
a role of NMDA receptors in it), oxidative stress with ROS and
RNS production, inflammation and apoptosis. Moreover, we focus
on the impact of these pathophysiological changes on the
structure and development of the brain, especially on its regions:
corpus striatum and hippocampus. These brain changes of the
offspring lead to impairments in their postnatal growth and
sensorimotor development, and in their motor functions, activity,
emotionality and learning ability in adulthood. Later we compare
various animal models used to investigate the impact of prenatal
and postnatal injury (hypoxic, ischemic or combinatory) on living
organisms, and show their advantages and limitations.
Huntington’s disease (HD) is a demential, neurodegenerative inheritable disease affecting middle-aged patients. HD is characterized by uncontrolled choreiform movements, psychiatric symptoms and cognitive decline. Histopathological changes in HD brains reveal a considerable damage to basal ganglia, particularly affecting middle-sized spiny neurons from the caudate-putamen region. Neurochemical changes are specifically oriented to deplete GABAergic and cholinergic systems, while molecular alterations include an increased expression of CAG trinucleotide at exon 1 from the huntingtin (htt) gene, as well as aggregation of mutant htt. Although several hypotheses regarding the mechanisms by which neurotoxicity is triggered in HD brains have been suggested on the basis of experimental evidence, so far it remains not clear which of them are predominant or whether they are complementary. Recent experimental evidence through transgenic mice models reveal an interesting inter action between expanded CAG triplets, mutant htt, and the increase in toxic metabolites from the kynurenine pathway. Further evidence supports the assumption that different toxic mechanisms (i.e. excitotoxicity, energy metabolism impairment, inflammatory events, oxidative stress, etc.) are confluent and depend on each other. In this review we will briefly summarize some of those findings and propose a final integrative hypothesis for HD., V. Pérez-de la Cruz, A. Santamaría., and Obsahuje bibliografii a bibliografické odkazy