[Performances of breast magnetic resonance imaging in the context of neoadjuvant chemotherapy for breast cancer to predict pathological complete response]. / Performances de l'imagerie par résonance magnétique au cours des chimiothérapies néoadjuvantes du cancer du sein pour prédire la réponse pathologique complète.

PURPOSE: The objective of this work was to estimate the reliability of MRI after neoadjuvant chemotherapy (NAC) for breast cancer to detect a residual tumour by comparing the tumoral size measured by MRI with the histological size. We also estimated the concordance of diagnosis of complete pathological response between histological examination and MRI. MATERIALS AND METHODS: We included all the patients who received a neoadjuvant chemotherapy for breast cancer in the university hospital of Tours from January, 2008 to December 31st, 2012 and in the comprehensive cancer centre of Rennes from January, 2008 till May 31st 201. We considered that the pathological response was complete (pCR) when there was no residual invasive tumour in the mammary surgical specimen. RESULTS: Two hundred and fifty-one women who received NAC for a non-metastatic breast cancer were included in the study: 103 in Tours and 148 in Rennes. Two women (0.8%) refused breast surgery whatever the type. One hundred and twenty-three (49%) women had a breast conservative surgery. One hundred and fifteen (45.8%) had a mastectomy and 11 (4.4%) had breast conservative surgery followed by mastectomy for positive margins. A complete pathological response was present in 54 cases (21.5%). We did not found any significant difference between characteristics of patients with pCR or not. CONCLUSION: Breast MRI remains the most performing examination to evaluate the initial tumoral size and the residual tumour after NAC, but does not add any value at mid or at the end of treatment for the patients to whom a mastectomy is decided at presentation. The correlation between the breast MRI and the histology size is not perfect, but at the moment, MRI stills of the most performing examination to predict the pCR.

Spreading depolarization triggered by elevated potassium is weak or absent in the rodent lower brain.

We examined in live coronal slices from rat and mouse which brain regions generate potassium-triggered spreading depolarization (SDKt). This technique simulates cortical spreading depression, which underlies migraine aura in the intact brain. An SDKt episode was evoked by increasing bath [K+]o and recorded as a propagating front of elevated light transmittance representing transient neuronal swelling in gray matter of neocortex, hippocampus, striatum, and thalamus. In contrast, SDKt was not imaged in hypothalamic nuclei or brainstem with exception of those nuclei near the dorsal brainstem surface. In rat slices, single neurons were whole-cell current clamped during SDKt. "Higher" neurons depolarized to near zero millivolts indicating SDKt generation. In contrast, seven types of neurons in hypothalamus and brainstem only slowly depolarized without generating SDKt, supporting our imaging findings. Therefore, SDKt is not a default of CNS neurons but rather displays a region-specific susceptibility, similar to anoxic depolarization, which we have proposed is correlated with a region's vulnerability to traumatic brain injury. In the higher brain, SDKt may be a vestigial spreading depolarization that originally evolved to shut down and vasoconstrict gray matter regions more exposed to impact and contusion.

Brainstem neurons survive the identical ischemic stress that kills higher neurons: insight to the persistent vegetative state.

Global ischemia caused by heart attack, pulmonary failure, near-drowning or traumatic brain injury often damages the higher brain but not the brainstem, leading to a 'persistent vegetative state' where the patient is awake but not aware. Approximately 30,000 U.S. patients are held captive in this condition but not a single research study has addressed how the lower brain is preferentially protected in these people. In the higher brain, ischemia elicits a profound anoxic depolarization (AD) causing neuronal dysfunction and vasoconstriction within minutes. Might brainstem nuclei generate less damaging AD and so be more resilient? Here we compared resistance to acute injury induced from simulated ischemia by 'higher' hippocampal and striatal neurons versus brainstem neurons in live slices from rat and mouse. Light transmittance (LT) imaging in response to 10 minutes of oxygen/glucose deprivation (OGD) revealed immediate and acutely damaging AD propagating through gray matter of neocortex, hippocampus, striatum, thalamus and cerebellar cortex. In adjacent brainstem nuclei, OGD-evoked AD caused little tissue injury. Whole-cell patch recordings from hippocampal and striatal neurons under OGD revealed sudden membrane potential loss that did not recover. In contrast brainstem neurons from locus ceruleus and mesencephalic nucleus as well as from sensory and motor nuclei only slowly depolarized and then repolarized post-OGD. Two-photon microscopy confirmed non-recoverable swelling and dendritic beading of hippocampal neurons during OGD, while mesencephalic neurons in midbrain appeared uninjured. All of the above responses were mimicked by bath exposure to 100 µM ouabain which inhibits the Na+/K+ pump or to 1-10 nM palytoxin which converts the pump into an open cationic channel. Therefore during ischemia the Na+/K+ pump of higher neurons fails quickly and extensively compared to naturally resilient hypothalamic and brainstem neurons. The selective survival of lower brain regions that maintain vital functions will support the persistent vegetative state.

A distinct boundary between the higher brain's susceptibility to ischemia and the lower brain's resistance.

Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na(+)/K(+) pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K(+)]o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.

A neuronal population in hypothalamus that dramatically resists acute ischemic injury compared to neocortex.

Pyramidal neurons (PyNs) of the cortex are highly susceptible to acute stroke damage, yet "lower" brain regions like hypothalamus and brain stem better survive global ischemia. Here we show for the first time that a "lower" neuron population intrinsically resists acute strokelike injury. In rat brain slices deprived of oxygen and glucose (OGD), we imaged anoxic depolarization (AD) as it propagated through neocortex or hypothalamus. AD, the initial electrophysiological event of stroke, is a front of depolarization that drains residual energy in compromised gray matter. The extent of AD reliably determines ensuing cortical damage, but do all CNS neurons generate a robust AD? During 10 min of OGD, PyNs depolarize without functional recovery. In contrast, magnocellular neuroendocrine cells (MNCs) in hypothalamus under identical stress generate a weak and delayed AD, resist complete depolarization, and rapidly repolarize when oxygen and glucose are restored. They recover their membrane potential, input resistance, and spike amplitude and can survive multiple OGD exposures. Two-photon microscopy in slices derived from a fluorescent mouse line confirms this protection, revealing PyN swelling and dendritic beading after OGD, whereas MNCs are not injured. Exposure to the Na(+)-K(+)-ATPase inhibitor ouabain (100 µM) induces AD similar to OGD in both cell types. Moreover, elevated extracellular K(+) concentration ([K(+)](o)) evokes spreading depression (SD), a milder version of AD, in PyNs but not MNCs. Therefore overriding the pump by OGD, ouabain, or elevated [K(+)](o) evokes a propagating depolarization in higher gray matter but not in MNCs. We suggest that variation in Na(+)-K(+)-ATPase pump efficiency during ischemia injury determines whether a neuronal type succumbs to or resists stroke.