## 3 Results
### Findings
#### 3.2.4 Neurovasculature  
Neurovascular abnormalities in epilepsy include changes in blood flow due to dysfunctional neuromuscular coupling, increased permeability of the blood-brain barrier, oxidative stress, and a more recent focus on disbalances in angiogenesis [67; 68]. We found six studies evaluating pathological activity-induced changes in the neurovasculature, visualizing the neurovasculature and vascular responses to ictal or interictal activity [60].  
[PERSON] et al. in 2017 [58] were able to quantify oxygen partial pressure in epileptic foci with 2 PI, showing a decreased partial oxygen pressure surrounding small arterioles during epileptic activity. [PERSON] et al. in 2019 [57] also correlated observed vessel responses with astrocytic Ca2+ activity. Increases in [Ca2+] were associated with vasodilation at the focus during ictal events, whereas in distal areas, increases in [Ca2+] were associated with vasoconstriction at the onset of a seizure and vasodilation at a later point during seizures. 2 PI was of notable value to these studies, as it allowed for high-resolution visualization of subtle processes, such as vasoconstriction and vasodilation. Additionally, [PERSON] et al. [21] were able to accurately monitor the build-up of lipofuscin in pial arteries of human epileptic tissue using three-dimensional two-photon fluorescence lifetime microscopy. The autofluorescence1 lipofuscin, an end-product of oxidative stress, was identified and quantified, indicating a role of oxidative stress in epilepsy.  
[PERSON] et al. [60] used 2 PI to visualize and quantify the flow of red blood cells in capillaries in vivo, yielding 2 PI measurements of blood flow. They reported that induced interictal activity resulted in increased blood flow to the interictal focus relative to distant regions. [PERSON] et al. [59] described a novel phenomenon found using 2 PI, wherein ictal events were preceded by vasoconstriction of vessels in regions distal from the focus. In response to seizures, however, vessels were found to dilate, with increasing degrees of dilation when more proximal to the focus. In terms of temporal characteristics, vasodilation in the focus occurred almost immediately after seizure onset whereas preictal vasoconstriction of vessels in distal regions occurred 5.3 \(\pm\) 0.5 s before seizure onset (see Figure 4). Preictal vasoconstriction was also observed in the study by [PERSON] et al. [61], and this was found to be correlated with increased excitatory and reduced inhibitory neuronal activity levels, as shown with [Ca2+] 2 PI.  
Figure 3: In vivo two-photon images of astrocytes in control mice (Ctrl, **left**) and KA-induced status epilepticus mice (KA, **right**) at several time points (**A: baseline, B–F: corresponding time from induction**). The images depict seizure-induced changes in astrocyte morphology (vacuolization and decreased average cell sizes). The white arrows show tracked astrocytes. Under normal conditions (Ctrl, **left**), astrocytes have a consistent appearance and thin processes, with no significant changes in fluorescence, number, or cell size occurring over a one-week period (Ctrl, **A–F**). On the other hand, KA-induced seizures (KA, **right**) resulted in cell vacuolization and astrogliosis at the one-week time point (KA, **A–F**). In addition, astrocytes underwent a reduction in average cell size and astrocytic processes appeared more prominent and extensive (KA, **F**). Scale bars: 50 \(\upmu\)m. Adapted from “Rapamycin attenuates acute seizure-induced astrocyte injury in mice in vivo” ([PERSON] et al., _Scientific Reports_, 2017 [49]). This figure has been modified. Creative Commons license: [[https://creativeccommons.org/licenses/by/4.0/](https://creativeccommons.org/licenses/by/4.0/)]([https://creativeccommons.org/licenses/by/4.0/](https://creativeccommons.org/licenses/by/4.0/)) (accessed on 17 November 2020).