Scalp hair repigmentation in the penumbral region of radiotherapy– a case series

Introduction: Hair colour is determined by varying ratios of black-brown eumelanin and reddish-brown/reddish-yellow pheomelanin. Hair colour change has been reported with cancer therapies. Radiotherapy (RT) usually causes temporary epilation to permanent alopecia. A change in hair colour following radiation is rare and usually results in depigmentation. There has only been one other case reported of repigmentation after RT. Cases: We present five cases of changes to scalp hair pigmentation in the penumbral region in patients treated with volumetric modulated arc therapy (VMAT) for skin cancer. Five treated areas across four patients involved repigmentation from grey to black, and there was one case of depigmentation from brown to grey. The latter occurred during immunotherapy administration. For the two cases where recalculation of the dosimetry was possible for three areas, repigmentation changes happened at an average mean dose of 16 Gy (9.3 – 26 Gy) in an average of 26 (25 - 27) fractions; that is, 0.6 Gy per fraction at five fractions per week. Discussion: This series of six areas in five patients of hair colour change in the penumbral region of VMAT to the scalp for skin cancer is the first report of this phenomenon. Repigmentation of scalp hair with RT is rare. Even though rare, the potential for hair colour change may need to be part of the informed consent discussion in patients contemplating this treatment.

LPDs – «Linked to Penumbra» Discharges or EEG Correlate of Excitotoxicity: A Review Based Hypothesis

Periodic lateralized epileptiform discharges (PLEDs) or lateralized periodic discharges (LPDs) are a well-known variant of pathological EEG activity. However, the mechanisms underpinning the appearance of this pattern are not completely understood. The heterogeneity of the features derived from LPDs patterns, and the wide range of pathological conditions in which they occur, raise a question about the unifying mechanisms underlying these phenomena. This paper reassesses the current opinion surrounding LPDs which considers glutamate excitotoxicity to be the primary pathophysiological basis, and the penumbral region to be the main morphological substrate. Arguments in favour of this hypothesis are presented, with interpretations supported by evidence from recent literature involving clinical and experimental data. Presently, no single hypothesis places considerable emphasis on the pathochemical properties of LPDs, which are implicitly meaningful towards better understanding of the clinical significance of this pattern.

Glucocorticoid receptors function in the pathophysiology of brain hypoxia

Glucocorticoid receptors are ligand-activated transcription factors, which play an important role in the brain, mainly in stress response regulation. There are two types of receptors for glucocorticosteroids: mineralocorticoid receptors (MR) with high-affinity for the ligands and glucocorticoid receptors (GR) with a tenfold lower affinity. Selective activation of the receptors during hypoxia may decide neuronal fate, especially in the hippocampus. Depending on the severity of hypoxia-induced damage, neurons undergo necrosis or apoptosis. In the penumbral region, where neurons die mainly through the process of apoptosis, selective GR activation increases excitotoxicity, interferes with apoptotic signalling pathways and causes energy deficit in the cells, all of which promote cell death. On the other hand, selective MR activation seems to be neuroprotective. It is suggested that the main role of MR in neuroprotection is to regulate the balance between anti- and proapoptotic proteins from bcl-2 family.

The 3D structure of the penumbra at high resolution from the bottom of the photosphere to the middle chromosphere

Sunspots are the most prominent feature of the solar magnetism in the photosphere. Although they have been widely investigated in the past, their structure remains poorly understood. Indeed, due to limitations in observations and the complexity of the magnetic field estimation at chromospheric heights, the magnetic field structure of sunspot above the photosphere is still uncertain. Improving the present knowledge of sunspot is important in solar and stellar physics, since spot generation is seen not only on the Sun, but also on other solar-type stars. In this regard, we studied a large, isolated sunspot with spectro-polarimeteric measurements that were acquired at the Fe I 6173 nm and Ca II 8542 nm lines by the spectropolarimeter IBIS/DST under excellent seeing conditions lasting more than three hours. Using the Non-LTE inversion code NICOLE, we inverted both line measurements simultaneously, to retrieve the three-dimensional magnetic and thermal structure of the penumbral region from the bottom of the photosphere to the middle chromosphere. Our analysis of data acquired at spectral ranges unexplored in previous studies shows clear spine and intra-spine structure of the penumbral magnetic field at chromopheric heights. Our investigation of the magnetic field gradient in the penumbra along the vertical and azimuthal directions confirms results reported in the literature from analysis of data taken at the spectral region of the He I 1083 nm triplet.

8e Protects against Acute Cerebral Ischemia by Inhibition of PI3Kγ-Mediated Superoxide Generation in Microglia

The inflammatory response mediated by microglia plays a critical role in the progression of ischemic stroke. Phosphoinositide 3-kinase gamma (PI3Kγ) has been implicated in multiple inflammatory and autoimmune diseases, making it a promising target for therapeutic intervention. The aim of this study was to evaluate the efficacy of 8e, a hydrogen sulfide (H2S) releasing derivative of 3-n-butylphthalide (NBP), on brain damage and PI3Kγ signaling following cerebral ischemia injury. 8e significantly reduced sensorimotor deficits, focal infarction, brain edema and neural apoptosis at 72 h after transient middle cerebral artery occlusion (tMCAO). The NOX2 isoform of the NADPH oxidase family is considered a major enzymatic source of superoxide. We found that the release of superoxide, together with the expression of NOX2 subunits p47phox, p-p47phox, and the upstream PI3Kγ/AKT signaling were all down-regulated by 8e, both in the penumbral region of the rat brain and in the primary cultured microglia subjected to oxygen-glucose deprivation (OGD). With the use of siRNA and pharmacological inhibitors, we further demonstrated that 8e regulates the formation of superoxide in activated microglia through the PI3Kγ/AKT/NOX2 signaling pathway and subsequently prevents neuronal death in neighboring neurons. Our experimental data indicate that 8e is a potential candidate for the treatment of ischemic stroke and PI3Kγ-mediated neuroinflammation.

The endovascular emergency treatment of an acute carotid artery dissection after Krav Maga training—a case report

Carotid artery dissection accounts for 20%–30% of all ischemic strokes in young patients aged <50 years. Recent guidelines on carotid disease management do not differentiate between traumatic and spontaneous dissection. We present a case of a 36-year-old male patient with the right internal carotid artery dissection treated with two XACT Abbot 6–8 mm × 40 mm stents placement after he was strangled during Krav Maga training. It is the most effective way to prevent the imminent stroke in the penumbral region. The safety and outcome of stent placement in internal carotid artery dissection remains unclear and further randomized trials are needed.

Painted Turtle Cortex is Resistant to an in Vitro Mimic of the Ischemic Mammalian Penumbra

Anoxia or ischemia causes hyperexcitability and cell death in mammalian neurons. Conversely, in painted turtle brain anoxia increases γ-amino butyric acid (GABA)ergic suppression of spontaneous electrical activity, and cell death is prevented. To examine ischemia tolerance in turtle neurons, we treated cortical sheets with an in vitro mimic of the penumbral region of stroke-afflicted mammalian brain (ischemic solution, IS). We found that during IS perfusion, neuronal membrane potential ( Vm) and the GABAA receptor reversal potential depolarized to a similar steady state (–92 ± 2 to −28 ± 3 mV, and −75 ± 1 to −35 ± 3 mV, respectively), and whole-cell conductance ( Gw) increased > 3-fold (from 4 ± 0.2 to 15 ± 1 nS). These neurons were electrically quiet and changes reversed after reperfusion. GABA receptor antagonism prevented the IS-mediated increase in Gw and neurons exhibited enhanced electrical excitability and rapid and irreversible rundown of Vm during reperfusion. These results suggest that inhibitory GABAergic mechanisms also suppress electrical activity in ischemic cortex. Indeed, after 4 hours of IS treatment neurons did not exhibit any apparent damage; while at 24 hours, only early indicators of apoptosis were present. We conclude that anoxia-tolerant turtle neurons are tolerant of exposure to a mammalian ischemic penumbral mimic solution.

Heterogeneity in the penumbra

Original experimental studies in nonhuman primate models of focal ischemia showed flow-related changes in evoked potentials that suggested a circumferential zone of low regional cerebral blood flow with normal K+ homeostasis, around a core of permanent injury in the striatum or the cortex. This became the basis for the definition of the ischemic penumbra. Imaging techniques of the time suggested a homogeneous core of injury, while positing a surrounding ‘penumbral’ region that could be salvaged. However, both molecular studies and observations of vascular integrity indicate a more complex and dynamic situation in the ischemic core that also changes with time. The microvascular, cellular, and molecular events in the acute setting are compatible with heterogeneity of the injury within the injury center, which at early time points can be described as multiple ‘mini-cores' associated with multiple ‘mini-penumbras’. These observations suggest the progression of injury from many small foci to a homogeneous defect over time after the onset of ischemia. Recent observations with updated imaging techniques and data processing support these dynamic changes within the core and the penumbra in humans following focal ischemia.

Cilostazol, a Phosphodiesterase Inhibitor, Attenuates Photothrombotic Focal Ischemic Brain Injury in Hypertensive Rats

The aim of this study was to evaluate and compare the effects of anti-platelet agents with different modes of action (cilostazol, aspirin, and clopidogrel) on brain infarction produced by photothrombotic middle-cerebral-artery (MCA) occlusion in male, spontaneously hypertensive rats. Cerebral blood flow (CBF) was measured with laser-Doppler flowmetry in the penumbral cortex. Infarct size was evaluated 24 h after MCA occlusion. The effects of these drugs on infarct size were examined by pretreatment of rats undergoing MCA occlusion. Pretreatment with cilostazol (100 mg/kg) significantly reduced infarct size. In contrast, aspirin (10 mg/kg) and clopidogrel (3 mg/kg) failed to mitigate infarct size, regardless of their apparent inhibitory effects on platelet aggregation. Post-treatment with cilostazol also significantly attenuated the infarct size, associated with improved CBF in the penumbral region. In support of this effect, cilostazol increased nitric oxide (NO) production and prostaglandin-I2 (PGI2) release in cultured human brain microvascular endothelial cells. Cilostazol-induced NO production and PGI2 release were completely abolished by an NO synthase inhibitor and aspirin, respectively. These findings show that cilostazol reduced brain infarct size due to an improvement in penumbral CBF possibly in association with increased endothelial NO and PGI2 production.

Alfvén waves in a gravitational field with flows

The gravitational stratification effect on magnetohydrodynamic waves at a single interface in the solar atmosphere has been studied in the penumbral region of the sunspot recently. The existence of slow and fast magneto acoustic gravity waves and their characteristics has been discussed. The effect of flows on magneto acoustic gravity surface waves leads to modes called flow modes or v-modes. The present geometry is that of a plasma slab moving with uniform velocity surrounded by a plasma of different density. As is applicable to the corona, we assume that the plasma β to be small. The dispersion characteristics change significantly with a change in the value of G (gravity) and uniform flow.