Background and Purpose-Focal stroke is associated with cell death, abnormal synaptic activity, and neurologic impairments. Given that many of these neuropathologic processes can be attributed to events that occur shortly after injury, it is necessary to understand how stroke affects the structure of neurons in surviving peri-infarct regions, particularly at the level of the dendritic spines, which transmit normal and potentially abnormal and injurious synaptic signaling. Recently, we described ischemia-induced changes in the structure of layer 1 dendritic tufts of transgenic mice expressing YFP in layer 5 cortical neurons. However, these in vivo imaging experiments could not address ischemia-related phenomena that occur in deeper cortical structures/layers, other cortical regions, or submicron changes in dendritic spine structure. Methods-Focal stroke was induced in the forelimb sensorimotor cortex by the photothrombotic method. Two,6,and 24 hours after stroke, brains were processed for Golgi-Cox staining to permit a detailed analysis of primary apical dendritic spine structure from layer 2/3 and 5 cortical pyramidal neurons. Results-Photothrombotic stroke caused a rapid deterioration of neurons, as revealed by Golgi-Cox labeling, in the infarct core that could be readily distinguished from surviving peri-infarct regions. Analysis of Ͼ15 000 dendritic spines revealed that although many spines were lost in the peri-infarct cortex during the first 24 hours after stroke (Ϸ38% lost), spines that remained were significantly longer (Ϸ25% at 6 hours). Furthermore, these effects were found in both layer 2/3 and 5 neurons and were restricted primarily to peri-infarct regions (Ͻ200 m from the infarct border). Key Words: neuronal plasticity Ⅲ penumbra Ⅲ excitotoxicity Ⅲ focal cerebral ischemia Ⅲ mice Ⅲ recovery T he sudden loss of blood flow to the brain (ie, ischemia) causes an immediate loss of cells in the ischemic core that is surrounded by an area of compromised, but potentially salvageable, tissue known as the penumbra, or peri-infarct region. 1 Because of this potential for rejuvenation, investigations have examined the physiologic changes that take place within the peri-infarct region during the first few hours and days after stroke. 2 For example, it is known that ischemia and reperfusion rapidly induce the production of reactive oxygen species, mitochondrial dysfunction, and glutamate release that is followed by repetitive spreading depression-like depolarizations and changes in intra-and extracellular loads of electrolytes (ie, calcium, potassium, zinc). 2-4 These abrupt changes in neuronal excitability and ionic homeostasis during the early stages of stroke could conceivably lead to extensive changes in the structure of peri-infarct neurons that may significantly affect their survival. Indeed, in vitro studies of oxygen/glucose deprivation or in vivo models of global ischemia have described acutely dysmorphic dendritic processes, spine loss, and filopodial formation within minutes of ischemia. [5][6][7] Recent ...

Diabetics are at greater risk of having a stroke and are less likely to recover from it. To understand this clinically relevant problem, we induced an ischemic stroke in the primary forelimb somatosensory (FLS1) cortex of diabetic mice and then examined sensory-evoked changes in cortical membrane potentials and behavioral recovery of forelimb sensory-motor function. Consistent with previous studies, focal stroke in non-diabetic mice was associated with acute deficits in forelimb sensorimotor function and a loss of forelimb evoked cortical depolarizations in peri-infarct cortex that gradually recovered over several weeks time. In addition, we discovered that damage to FLS1 cortex led to an enhancement of forelimb evoked depolarizations in secondary forelimb somatosensory (FLS2) cortex. Enhanced FLS2 cortical responses appeared to play a role in stroke recovery given that silencing this region was sufficient to reinstate forelimb impairments. By contrast, the functional reorganization of FLS1 and FLS2 cortex was largely absent in diabetic mice and could not be explained by more severe cortical infarctions. Diabetic mice also showed persistent behavioral deficits in sensorimotor function of the forepaw, which could not be rescued by chronic insulin therapy after stroke. Collectively these results indicate that diabetes has a profound effect on brain plasticity, especially when challenged, as is often the case, by an ischemic event. Further, our data suggest that secondary cortical regions play an important role in the restoration of sensorimotor function when primary cortical regions are damaged.

Calibrated pressure-flow (P-V) curves were plotted by computer using data from both the plethysmographic method for measuring airway resistance and the esophageal balloon technique for measuring lung resistance. P-V curves from 100 sick, healthy, and convalescent infants (age range 2 days to 19 months, weight range 0.9-10.4 kg) were classified into five distinctive types according to shape and direction of looping. Two of these patterns, one with a virtually closed, the other with a narrow figure-of-eight loop, reflected the normal physiologic changes in airway caliber that may occur during tidal breathing. The remaining three patterns, with far more marked changes in resistance, were associated with particular pathophysiologic mechanisms of airway obstruction. A wide figure-of-eight configuration, in which the expiratory loop rotated clockwise with marked flow limitation toward end expiration, was found for infants with chronic lung disease. By contrast, a rise in initial expiratory resistance due to dynamic glottic narrowing, with an anticlockwise rotated expiratory P-V loop, occurred in infants with reduced or unstable lung volumes. A clockwise inspiratory loop was observed only for infants intubated during the neonatal period, many of whom had clinical evidence of extrathoracic airway obstruction. Inspection and analysis of P-V curves provides more information about the state of the airways than does a single numerical expression of resistance. However, since normal patterns of P-V curves are not restricted to infants with healthy airways, a combined qualitative and quantitative approach to these measurements is recommended.

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