Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_24_библиотеки_им_акад_М_И_Перельмана

Florenzano et al. 2008). In the cerebellar system, neuronal responses of axotomized neurons persists for approximately 2months, during which the olivary and pontine neuronal cell populations progressively fade (Buffo et al. 1998; Viscomi etal. 2004). However, before dying for apoptotic cell death (Viscomi etal. 2009b), Pn and IO neurons present a series of morphological changes such as chromatolysis, reduction of basophilic cytoplasmic substances, nuclear eccentricity, nuclear and nucleolar enlargement, cell swelling, and retrac­tion of dendrites. Days, weeks, or months after injury onset, the interplay between key mechanisms of life/death decisions such as oxidative damage (Oddi et al. 2012), apoptosis (Viscomi etal. 2009b), inammation (Viscomi etal. 2008a, b; Bisicchia et al. 2018), and autophagy (Viscomi etal. 2012; Viscomi and D’Amelio 2012) that differentially affects sur­vival of axotomized neurons.

With regard to anatomical brain organization after HCb, the developmental time frame during which a lesion devel­ops highly inuences postlesional brain plasticity (Castro

1978). When HCb is performed early in development it

induces rewiring not only in spared cerebellar efferents, but also in systems that project to the cerebellar stations. Neonatal HCb is associated with anomalous increases in crossed sensorimotor cortico-pontine (O’Donoghue et al.

1987) and rubro-olivary projections (Swenson and Castro

showed a tendency toward “high stepping.” Their steps were regular and symmetrical but hypometric. Adult lesioned ani­mals displayed a marked extensor hypotonia, ipsilateral to the lesion during stance and a relevant hyperexion affecting both sides, during swing. Alteration of the interlimb coordi­nation and modied sequence of steps were also observed. Thus, adult lesioned animals displayed a highly asymmetri­cal, impaired and unstable locomotion than young animals.

Nevertheless, in adulthood, a prolonged exposure to an enriched environment can exert benecial effects on both motor and cognitive symptoms induced by HCb (Foti etal.

2014), providing clear and promising evidence for new neu-

Alcohol (EtOH) is a socially accepted and widely used psychoactive compound, derived from the fermentation/ distillation of various plant sugars. Despite its wide use and acceptance, EtOH is a highly addictive and extremely harmful substance. Indeed, the American Psychiatric Society’s, “Diagnostic and Statistical Manual of Mental Disorders” includes the diagnosis of “alcohol use disor­der” (AUD) based on the presence of a range of harmful interactions with alcohol, including abuse and addiction/ dependence. Alcohol abuse alone is the third leading pre­ventable cause of death in the United States, via accidents, but also increased risk for various other harmful condi­tions such as brain damage, cancer and heart disease. In addition to its harm to the user, alcohol abuse is a main contributing factor in harm to others via its role in trafc fatalities and approximately 33% of cases of domestic violence. EtOH is an unusual psychoactive drug in that despite having multiple behavioral and psychological effects, EtOH does not have well-dened specic molec­ular targets. Instead, EtOH appears to affect multiple molecular, cellular and synaptic systems, with the number of neural systems affected increasing with increasing con­centrations of EtOH.Importantly the various neural tar­gets and associated brain regions are differentially affected by increasing concentrations of alcohol, and a fair number of neural systems are not notably affected by recreational or even abusive concentrations of EtOH.

For reference throughout this chapter, Fig.68.1 is a schematic circuit diagram of the cerebellum, showing the two excitatory/glutamatergic afferent inputs to the cerebellar cor­tex (mossy bers and climbing bers), the connectivity of the interneurons, which include the glutamatergic granule cells (GCs), GABAergic Golgi cells and Molecular Layer interneu­rons (MLIs), and the sole output of the cerebellar cortex, the GABAergic Purkinje cells (PCs). The PCs synapse onto a variety of cells distributed into three cerebellar nuclei, which in turn, in addition to long-known motor- related outputs to thalamus and spinal cord (not depicted), send mono and poly­synaptic efferents to most of the rest of the brain.

2014; Nikolaou et al. 2013a, b; Bjork and Gilman 2014;