A functional observational battery for evaluation of neurological outcomes in a rat model of acute bacterial meningitis
(2020) In Intensive Care Medicine Experimental 8.- Abstract
- Background
Acute bacterial meningitis is a disease with a high mortality and a high incidence of neurological sequelae in survivors. There is an acute need to develop new adjuvant therapies. To ensure that new therapies evaluated in animal models are translatable to humans, studies must evaluate clinically relevant and patient-important outcomes, including neurological symptoms and sequelae.
Methods
We developed and tested a functional observational battery to quantify the severity of a variety of relevant neurological and clinical symptoms in a rat model of bacterial meningitis. The functional observational battery included symptoms relating to general clinical signs, gait and posture abnormalities, involuntary motor... (More) - Background
Acute bacterial meningitis is a disease with a high mortality and a high incidence of neurological sequelae in survivors. There is an acute need to develop new adjuvant therapies. To ensure that new therapies evaluated in animal models are translatable to humans, studies must evaluate clinically relevant and patient-important outcomes, including neurological symptoms and sequelae.
Methods
We developed and tested a functional observational battery to quantify the severity of a variety of relevant neurological and clinical symptoms in a rat model of bacterial meningitis. The functional observational battery included symptoms relating to general clinical signs, gait and posture abnormalities, involuntary motor movements, focal neurological signs, and neuromotor abnormalities which were scored according to severity and summed to obtain a combined clinical and neurological score. To test the functional observational battery, adult Sprague-Dawley rats were infected by intracisternal injection of a clinical isolate of Streptococcus pneumoniae. Rats were evaluated for 6 days following the infection.
Results
Pneumococcal meningitis was not lethal in this model; however, it induced severe neurological symptoms. Most common symptoms were hearing loss (75% of infected vs 0% of control rats; p = 0.0003), involuntary motor movements (75% of infected vs 0% of control rats; p = 0.0003), and gait and posture abnormality (67% of infected vs 0% of control rats; p = 0.0013). Infected rats had a higher combined score when determined by the functional observational battery than control rats at all time points (24 h 12.7 ± 4.0 vs 4.0 ± 2.0; 48 h 17.3 ± 7.1 vs 3.4 ± 1.8; 6 days 17.8 ± 7.4 vs 1.7 ± 2.4; p < 0.0001 for all).
Conclusions
The functional observational battery described here detects clinically relevant neurological sequelae of bacterial meningitis and could be a useful tool when testing new therapeutics in rat models of meningitis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/e28cb5a6-9b64-4d63-89a6-fdc04b7481f8
- author
- Fisher, Jane LU ; Pavan, Chiara LU ; Ohlmeier, Luisa ; Nilson, Bo LU ; Lundgaard, Iben LU ; Linder, Adam LU and Bentzer, Peter LU
- organization
-
- Infection Medicine (BMC)
- Translational Sepsis research (research group)
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- Division of Medical Microbiology
- WCMM-Wallenberg Centre for Molecular Medicine
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Glia-Immune Interactions (research group)
- Clinical Research in Anaesthesia and Intensive Care Medicine (research group)
- Fluid resuscitation in critical illness (research group)
- Anesthesiology and Intensive Care
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Intensive Care Medicine Experimental
- volume
- 8
- article number
- 40
- publisher
- Springer
- external identifiers
-
- pmid:32770475
- scopus:85117765230
- ISSN
- 2197-425X
- DOI
- 10.1186/s40635-020-00331-1
- language
- English
- LU publication?
- yes
- id
- e28cb5a6-9b64-4d63-89a6-fdc04b7481f8
- date added to LUP
- 2020-08-14 11:07:13
- date last changed
- 2023-04-05 15:04:20
@article{e28cb5a6-9b64-4d63-89a6-fdc04b7481f8, abstract = {{Background<br> Acute bacterial meningitis is a disease with a high mortality and a high incidence of neurological sequelae in survivors. There is an acute need to develop new adjuvant therapies. To ensure that new therapies evaluated in animal models are translatable to humans, studies must evaluate clinically relevant and patient-important outcomes, including neurological symptoms and sequelae.<br> <br> Methods<br> We developed and tested a functional observational battery to quantify the severity of a variety of relevant neurological and clinical symptoms in a rat model of bacterial meningitis. The functional observational battery included symptoms relating to general clinical signs, gait and posture abnormalities, involuntary motor movements, focal neurological signs, and neuromotor abnormalities which were scored according to severity and summed to obtain a combined clinical and neurological score. To test the functional observational battery, adult Sprague-Dawley rats were infected by intracisternal injection of a clinical isolate of Streptococcus pneumoniae. Rats were evaluated for 6 days following the infection.<br> <br> Results<br> Pneumococcal meningitis was not lethal in this model; however, it induced severe neurological symptoms. Most common symptoms were hearing loss (75% of infected vs 0% of control rats; p = 0.0003), involuntary motor movements (75% of infected vs 0% of control rats; p = 0.0003), and gait and posture abnormality (67% of infected vs 0% of control rats; p = 0.0013). Infected rats had a higher combined score when determined by the functional observational battery than control rats at all time points (24 h 12.7 ± 4.0 vs 4.0 ± 2.0; 48 h 17.3 ± 7.1 vs 3.4 ± 1.8; 6 days 17.8 ± 7.4 vs 1.7 ± 2.4; p < 0.0001 for all).<br> <br> Conclusions<br> The functional observational battery described here detects clinically relevant neurological sequelae of bacterial meningitis and could be a useful tool when testing new therapeutics in rat models of meningitis.}}, author = {{Fisher, Jane and Pavan, Chiara and Ohlmeier, Luisa and Nilson, Bo and Lundgaard, Iben and Linder, Adam and Bentzer, Peter}}, issn = {{2197-425X}}, language = {{eng}}, publisher = {{Springer}}, series = {{Intensive Care Medicine Experimental}}, title = {{A functional observational battery for evaluation of neurological outcomes in a rat model of acute bacterial meningitis}}, url = {{http://dx.doi.org/10.1186/s40635-020-00331-1}}, doi = {{10.1186/s40635-020-00331-1}}, volume = {{8}}, year = {{2020}}, }