Objectives: We investigated whether seizure susceptibility increases over weeks–months after experimental traumatic brain injury (TBI), and whether seizure susceptibility in rats predicts the development of post-traumatic epilepsy (PTE) or epileptiform activity. We further investigated whether rats develop chronic sleep disturbance after TBI, and whether sleep disturbance parameters—alone or in combination with pentylenetetrazol (PTZ) test parameters—could serve as novel biomarkers for the development of post-traumatic epileptogenesis. Methods: TBI was induced in adult male Sprague-Dawley rats with lateral fluid-percussion injury. Sham-operated experimental controls underwent craniectomy without exposure to an impact force. Seizure susceptibility was tested with a PTZ test (30 mg/kg, intraperitoneally) on day (D) 30, D60, D90, and D180 after TBI (n = 28) or sham operation (n = 16) under video electroencephalogram (vEEG). In the 7th post-injury month, rats underwent continuous vEEG monitoring to detect spontaneous seizures and assess sleep disturbances. At the end of the experiments, rats were perfused for brain histology. Results: In the TBI group, the percentage of rats with PTZ-induced seizures increased over time (adjusted p < 0.05 compared with D30). Combinations of three PTZ test parameters (latency to the first epileptiform discharge (ED), number of EDs, and number of PTZ-induced seizures) survived the leave-one-out validation for differentiating rats with or without epileptiform activity, indicating an area under the receiver operating curve (AUC) of 0.743 (95% CI 0.472–0.992, p = 0.05) with a misclassification rate of 36% on D90, and an AUC of 0.752 (95% CI 0.483–0.929, p < 0.05) with a misclassification rate of 32% on D180. Sleep analysis revealed that the number of transitions to N3 or rapid eye movement (REM) sleep, along with the total number of transitions, was increased in the TBI group during the lights-on period (all p < 0.05). The sleep fragmentation index during the lights-on period was greater in the TBI rats than in sham-operated rats (p < 0.05). A combination of sleep parameters showed promise as diagnostic biomarkers of prior TBI, with an AUC of 0.792 (95% CI 0.549–0.934, p < 0.01) and a misclassification rate of 28%. Rats with epilepsy or any epileptiform activity had more transitions from N3 to the awake stage (p < 0.05), and the number of N3–awake transitions differentiated rats with or without epileptiform activity, with an AUC of 0.857 (95% CI 0.651–1.063, p < 0.01). Combining sleep parameters with PTZ parameters did not improve the biomarker performance. Significance: This is the first attempt to monitor the evolution of seizure susceptibility over months in a well-described rat model of PTE. Our data suggest that assessment of seizure susceptibility and sleep disturbance can provide diagnostic biomarkers of prior TBI and prognostic biomarkers of post-traumatic epileptogenesis.

Disabilities resulting from traumatic brain injury (TBI) strongly correlate with the cytoarchitectonic part of the brain damaged, lesion area, and type of lesion. We developed a Web application to estimate the location of the lesion on mouse cerebral cortex caused by TBI induced by lateral fluid-percussion injury. The application unfolds user-determined TBI lesion measurements, e.g., from histologic sections to a reference template, and estimates the total lesion area, including the percentage of cortex damaged in different cytoarchitectural cortical regions. The resulting lesion can be visualized on a two-dimensional map of mouse cerebral cortex. The application also visualizes the development of the lesion over time when measurements from multiple time points are available. The web application was validated by comparing its performance to the manual method. The total area of the cortical lesion was similar between the manual (9.19 ± 0.66 mm 2 , range 4.25-14.93 mm 2) and the automated analysis (9.27 ± 0.66 mm 2 , range 4.50-15.10 mm 2) (p = 0.938). The results of the manual and automated analyses were strongly correlated (r = 0.999, p < 0.0001, Pearson correlation). The lesion localized in the same cytoarchitectonic regions when the unfolded map from the automated method was superimposed onto the map obtained using the manual method. The Web applicationautomated method is faster than the manual method in generating unfolded cortical lesion maps. The accuracy of the presented automated method in determining the anteroposterior level and outlining the lesion is equal to or greater than that of the manual method. Our application provides a novel tool for accurately quantifying and visualizing TBI lesions on mouse cerebral cortex.

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Objectives: To explore the opinions, the usage and the patient education given on nasal saline irrigation by physicians and pharmaceutical personnel working in Finland. Design: An internet-based survey with predetermined, multiple-choice answers. Setting: Primary care centres, occupational health centres and private care centres in Eastern Finland as well as pharmacies in Finland. Main outcome measures: Healthcare professionals views, practice and general knowledge of nasal irrigation for sinonasal symptoms and conditions. Results: We received 595 completed surveys (110 physicians, 485 pharmacists). The majority of the respondents recommended nasal saline irrigation for their patients either as a symptomatic treatment (98.0%) or to treat a specific condition (97.5%) such as acute rhinosinusitis, chronic rhinosinusitis and allergic rhinitis. Nasal saline irrigation was also often recommended as a prophylaxis for airway-infections (71.9%) and to enhance the health of the nasal mucosa (58.2%). In general, the possible adverse effects were recognised poorly by both professions. There was a clear difference between the two professions, as physicians were more conservative in recommending nasal saline irrigation and recognised possible adverse effects, such as epistaxis, pain, and dryness of the nose, better (75% vs. 59%, p ¼ 0.002). Conclusions: Nasal saline irrigation seems to be a popular treatment recommended by many health care professionals in Finland. Physicians and pharmaceutical personnel had variable opinions on the indications, utility and risks of nasal saline irrigation. There are also clear differences between physicians and pharmaceutical personnel's practices. There is a need to better educate professionals about nasal saline irrigation and to further study whether nasal saline irrigation is efficient and safe option for the different common sinonasal conditions. KEY POINTS Little information is available on how physicians and pharmacists recommend nasal saline irrigation as a symptomatic treatment. Physicians and pharmacists seem to have variable opinions about the indications, utility and safety of nasal saline irrigation. The patient education given is in general very heterogenous. Both professions require more education to ensure that the usage remains as safe as possible for the patient.