Cognitive and linguistic dysfunction after thalamic stroke and recovery process: possible mechanism

<abstract> <p>Thalamic stroke may result in cognitive and linguistic problems, but the underlying mechanism remains unknown. Especially, it is still a matter of debate why thalamic aphasia occasionally occurs and then mostly recovers to some degree. We begin with a brief overview of the cognitive dysfunction and aphasia, and then review previous hypotheses of the underlying mechanism. We introduced a unique characteristic of relatively transient “word retrieval difficulty” of patients in acute phase of thalamic stroke. Word retrieval ability involves both executive function and speech production. Furthermore, SMA aphasia and thalamic aphasia may resemble in terms of the rapid recovery, thus suggesting a shared neural system. This ability is attributable to the supplementary motor area (SMA) and inferior frontal cortex (IFG) via the frontal aslant tract (FAT). To explore the possible mechanism, we applied unique hybrid neuroimaging techniques: single-photon emission computed tomography (SPECT) and functional near-infrared spectroscopy (f-NIRS). SPECT can visualize the brain distribution associated with word retrieval difficulty, cognitive disability or aphasia after thalamic stroke, and f-NIRS focuses on SMA and monitors long-term changes in hemodynamic SMA responses during phonemic verbal task. SPECT yielded common perfusion abnormalities not only in the fronto–parieto–cerebellar–thalamic loop, but also in bilateral brain regions such as SMA, IFG and language-relevant regions. f-NIRS demonstrated that thalamic stroke developed significant word retrieval decline, which was intimately linked to posterior SMA responses. Word retrieval difficulty was rapidly recovered with increased bilateral SMA responses at follow-up NIRS. Together, we propose that the cognitive domain affected by thalamic stroke may be related to the fronto–parieto–cerebellar–thalamic loop, while the linguistic region may be attributable to SMA, IFG and language-related brain areas. Especially, bilateral SMA may play a crucial role in the recovery of word retrieval, and right language-related region, including IFG, angular gyrus and supramarginal gyrus may determine recovery from thalamic aphasia.</p> </abstract>

Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity

<abstract> <p>Gamma-aminobutyric acid (GABA) acts on ventromedial hypothalamic targets to suppress counter-regulatory hormone release, thereby lowering blood glucose. Maladaptive up-regulation of GABA signaling is implicated in impaired counter-regulatory outflow during recurring insulin-induced hypoglycemia (RIIH). Ventromedial hypothalamic nucleus (VMN) GABAergic neurons express the sensitive energy gauge 5′-AMP-activated protein kinase (AMPK). Current research used high-neuroanatomical resolution single-cell microdissection tools to address the premise that GABAergic cells in the VMNvl, the primary location of ‘glucose-excited’ metabolic-sensory neurons in the VMN, exhibit attenuated sensor activation during RIIH. Data show that during acute hypoglycemia, VMNvl glutamate decarboxylase_65/67 (GAD)-immunoreactive neurons maintain energy stability, yet a regional subset of this population exhibited decreased GAD content. GABA neurons located along the rostrocaudal length of the VMNvl acclimated to RIIH through a shift to negative energy imbalance, e.g. increased phosphoAMPK expression, alongside amplification/gain of inhibition of GAD profiles. Acquisition of negative GAD sensitivity may involve altered cellular receptivity to noradrenergic input via α₂-AR and/or β₁-AR. Suppression of VMNvl GABA nerve cell signaling during RIIH may differentiate this neuroanatomical population from other, possibly non-metabolic-sensory GABA neurons in the MBH. Data here also provide novel evidence that VMNvl GABA neurons are direct targets of glucocorticoid control, and show that glucocorticoid receptors may inhibit RIIH-associated GAD expression in rostral VMNvl GABAergic cells through AMPK-independent mechanisms.</p> </abstract>

Tumor necrosis factor (TNF) induces astrogliosis, microgliosis and promotes survival of cortical neurons

<abstract><sec> <title>Objectives</title> <p>Neuro-inflammation occurs as a sequence of brain injury and is associated with production of cytokines. Cytokines can modulate the function and survival of neurons, microglia and astrocytes. The objective of this study is to examine the effect of TNF on the neurons, microglia and astrocytes in normal brain and stab wound brain injury.</p> </sec><sec> <title>Methods</title> <p>Normal BALB/c male mice (N) without any injury were subdivided into NA and NB groups. Another set mouse was subjected to stab wound brain injury (I) and were subdivided into IA and IB. NA and IA groups received intraperitoneal injections of TNF (1 µg/kg body weight/day) for nine days, whereas NB and IB groups received intraperitoneal injections of PBS. Animals were killed on 1^st, 2^nd, 3^rd, 7^th, and 9^th day. Frozen brain sections through the injury site in IA and IB or corresponding region in NA and NB groups were stained for neurodegeneration, immunostained for astrocytes, microglia and neurons. Western blotting for GFAP and ELISA for BDNF were done from the tissues collected from all groups.</p> </sec><sec> <title>Results</title> <p>The number of degenerating neurons significantly decreased in TNF treated groups. There was a significant increase in the number of astrocytes and microglia in TNF treated groups compared to PBS treated groups. In addition, it was found that TNF stimulated the expression of GFAP and BDNF in NA and IA groups.</p> </sec><sec> <title>Conclusions</title> <p>TNF induces astrogliosis and microgliosis in normal and injured brain and promotes the survival of cortical neurons in stab wound brain injury, may be by upregulating the BDNF level.</p> </sec></abstract>