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A functional observational battery for evaluation of neurological outcomes in a rat model of acute bacterial meningitis

Fisher, Jane LU ; Pavan, Chiara LU ; Ohlmeier, Luisa ; Nilson, Bo LU orcid ; Lundgaard, Iben LU ; Linder, Adam LU and Bentzer, Peter LU (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)
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author
; ; ; ; ; and
organization
publishing date
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 &lt; 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}},
}