Hypoxia and Hypotension Transform the Blood Flow Response to Cortical Spreading Depression from Hyperemia into Hypoperfusion in the Rat

Experimental and clinical studies indicate that waves of cortical spreading depolarization (CSD) appearing in the ischemic penumbra contribute to secondary lesion growth. We used an embolic stroke model that enabled us to investigate inverse coupling of blood flow by laser speckle imaging (CBF LSF ) to CSD as a contributing factor to lesion growth already in the early phase after arterial occlusion. Embolization by macrospheres injected into the left carotid artery of anesthetized rats reduced CBF LSF in the territories of the middle cerebral artery (MCA) (8/14 animals), the posterior cerebral artery (PCA) (2/14) or in less clearly defined regions (4/14). Analysis of MCA occlusions (MCAOs) revealed a first CSD wave starting off during ischemic decline at the emerging core region, propagating concentrically over large portions of left cortex. Subsequent recurrent waves of CSD did not propagate concentrically but preferentially circled around the ischemic core. In the vicinity of the core region, CSDs were coupled to waves of predominantly vasoconstrictive CBF LSF responses, resulting in further decline of CBF in the entire inner penumbra and in expansion of the ischemic core. We conclude that CSDs and corresponding CBF responses follow a defined spatiotemporal order, and contribute to early evolution of ischemic territories.

Section: Discussionmentioning

confidence: 99%

Distinct Spatiotemporal Patterns of Spreading Depolarizations during Early Infarct Evolution: Evidence from Real-Time Imaging

Kumagai

Walberer

Nakamura

et al. 2010

“…As such, it is vitally important to elucidate the relationship between metabolic disruption, lactate, acidosis, and tissue damage. Finally, whereas our current study used a permanent stroke model to elucidate the correlation between tissue pH, diffusion, and lactic acidosis, it remains very promising to extend pH MRI to applications such as transient ischemic attack and cortical spreading depression in which the tissue pH change is dynamic and heterogeneous (Bisschops et al, 2002;Mutch and Hansen, 1984;Sukhotinsky et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Association between pH-Weighted Endogenous Amide Proton Chemical Exchange Saturation Transfer MRI and Tissue Lactic Acidosis during Acute Ischemic Stroke

Sun

Cheung

Wang

et al. 2011

129

139

The ischemic tissue becomes acidic after initiation of anaerobic respiration, which may result in impaired tissue metabolism and, ultimately, in severe tissue damage. Although changes in the major cerebral metabolites can be studied using magnetic resonance (MR) spectroscopy (MRS)-based techniques, their spatiotemporal resolution is often not sufficient for routine examination of fastevolving and heterogeneous acute stroke lesions. Recently, pH-weighted MR imaging (MRI) has been proposed as a means to assess tissue acidosis by probing the pH-dependent chemical exchange of amide protons from endogenous proteins and peptides. In this study, we characterized acute ischemic tissue damage using localized proton MRS and multiparametric imaging techniques that included perfusion, diffusion, pH, and relaxation MRI. Our study showed that pH-weighted MRI can detect ischemic lesions and strongly correlates with tissue lactate content measured by 1 H MRS, indicating lactic acidosis. Our results also confirmed the correlation between apparent diffusion coefficient and lactate; however, no significant relationship was found for perfusion, T 1 , and T 2 . In summary, our study showed that optimized endogenous pH-weighted MRI, by sensitizing to local tissue pH, remains a promising tool for providing a surrogate imaging marker of lactic acidosis and altered tissue metabolism, and augments conventional techniques for stroke diagnosis.

“…This is complementary to previous reports describing that deeper initial hypoperfusion of the CBF response coincides with longer ECoG depression, 18 and that longer duration of the initial hypoperfusion corresponds with longer DC shift duration with SD, in experimental models, as well as in patients of aneurysmal subarachnoid haemorrhage. 35,36 Taken together, a more prominent dilator component in the CBF response (i.e., smaller magnitude of initial hypoperfusion or larger amplitude of hyperemia) appears to facilitate the faster return of the cortex' electrical activity after the passage of SD.…”

Section: Distinct Features Of the Ecog Power Spectrummentioning

confidence: 99%

Advancing age and ischemia elevate the electric threshold to elicit spreading depolarization in the cerebral cortex of young adult rats

Hertelendy

Menyhárt

Makra

et al. 2016

Spreading depolarizations of long cumulative duration have been implicated in lesion development and progression in patients with stroke and traumatic brain injury. Spreading depolarizations evolve less likely in the aged brain, but it remains to be determined at what age the susceptibility to spreading depolarizations starts to decline, especially in ischemia. Spreading depolarizations were triggered by epidural electric stimulation prior and after ischemia induction in the cortex of 7-30 weeks old anesthetized rats (n ¼ 38). Cerebral ischemia was achieved by occlusion of both common carotid arteries. Spreading depolarization occurrence was confirmed by the acquisition of DC potential and electrocorticogram. Cerebral blood flow variations were recorded by laser-Doppler flowmetry. Dendritic spine density in the cortex was determined in Golgi-COX stained sections. Spreading depolarization initiation required increasingly greater electric charge with older age, a potential outcome of consolidation of cortical connections, indicated by altered dendritic spine distribution. The threshold of spreading depolarization elicitation increased with ischemia in all age groups, which may be caused by tissue acidosis and increased K þ conductance, among other factors. In conclusion, the brain appears to be the most susceptible to spreading depolarizations at adolescent age; therefore, spreading depolarizations may occur in young patients of ischemic or traumatic brain injury at the highest probability.