Apparatus and method for inducing epileptic seizures in test animals for anticonvulsant drug screening

• US 6,309,406 B1
• Filed: 11/24/1999
• Issued: 10/30/2001
• Est. Priority Date: 11/24/1999
• Status: Expired due to Fees

• Current Assignee: Hamit-Darwin-Fresh, Inc.
• Original Assignee: Hamit-Darwin-Fresh, Inc.
• Inventors: Jones, Gary L., Rainey, Robert R.
• Primary Examiner(s): Getzow, Scott M.
• Application Number:
  US09/448,719
• Time in Patent Office: 706 Days
• Field of Search: 607/2, 607/3, 607/45, 607/48, 607/58, 607/62, 607/66-76, 600/544, 600/545, 600/546
• US Class Current: 607/2
• CPC Class Codes: A61N 1/36017 with leads or electrodes penetrating the skin
• CPC Class Codes: A61N 1/36025 for treating a mental or cerebral condition
• CPC Class Codes: A61N 1/36082 Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease

Abstract

A stimulator for electrically inducing a maximal seizure in a test animal for screening candidate anticonvulsant drugs is disclosed. A stimulator according to this invention includes stimulus generation and control circuitry for generating the stimulus, a display for displaying the duration of three phases of the induced seizure, and user input configured to allow the user to control delivery of the stimulus and to record seizure phase transitions to be displayed on the display. The stimulator may also include a foot switch, electrodes, a computer interface and an optional computer. A method of measuring the phases of an electrically induced seizure is disclosed. A method of analyzing the efficacy of a candidate anticonvulsant drug is also disclosed.

Claims

1. A stimulator, comprising:

stimulus generation and control circuitry for providing an electrical stimulus sufficient to induce an epileptic seizure in a laboratory test animal;

a display, coupled to said stimulus generation and control circuitry, for displaying three phases of the electrically induced epileptic seizure; and

a user input device, coupled to said stimulus generation and control circuitry, configured for a user to control delivery of the electrical stimulus and enter epileptic seizure phase transition timing signals.

2. The stimulator of claim 1, wherein said stimulus generation and control circuitry comprises:

a power supply for providing a periodic source signal;

digital logic circuitry coupled to said power supply and said user input device for receiving selected parameters of said electrical stimulus;

a filter circuit coupled to said power supply and said digital logic circuitry for shaping said periodic source signal; and

a power amplifier coupled to said power supply, said digital logic circuitry and said filter circuit for receiving said shaped periodic source signal from said filter circuit and generating said electrical stimulus according to said selected parameters.

3. The stimulator of claim 1, wherein said display comprises:

a first timer for displaying elapsed time corresponding to a first phase of an epileptic seizure;

a second timer for displaying elapsed time corresponding to a second phase of an epileptic seizure; and

a third timer for displaying elapsed time corresponding to a third phase of an epileptic seizure.

4. The stimulator of claim 3, wherein said display further includes:

an activation time display for displaying the total duration time for said electrical stimulus.

5. The stimulator of claim 1, wherein said user input device includes a foot switch configured for selectively changing a state of operation of said stimulator.

6. The stimulator of claim 1, wherein said user input device includes controls for adjusting current delivered by said electrical stimulus and adjusting activation time of said electrical stimulus.

7. The stimulator of claim 1, further comprising a stimulus cable and electrodes for delivering said electrical stimulus to a test animal.

8. The stimulator of claim 7, wherein said electrodes are Spiegel electrodes.

9. A stimulator configured for inducing a maximal seizure in a test animal comprising:

a digital controller for controlling operations of the stimulator;

a stimulus generator coupled to said digital controller for providing a stimulus sufficient to induce a maximal seizure in a test animal; and

a display coupled to said digital controller configured for displaying operational status of said stimulator and seizure phase duration.

10. The stimulator of claim 9, wherein said digital controller includes at least three timer circuits.

11. The stimulator of claim 9, wherein said stimulus generator includes:

a filter coupled to said digital controller for converting a square wave input to a sine wave output; and

a power amplifier coupled to said digital controller and receiving said sine wave from said filter for amplifying the peak-to-peak voltage of said sine wave producing a stimulus.

12. The stimulator of claim 11, wherein said stimulus is approximately 60 Hz, with voltage ranging from about ±

240 volts, and current ranging between about 2 mA rms to about 250 mA rms.

13. The stimulator of claim 9, wherein said display includes at least three timer displays.

14. The stimulator of claim 13, wherein said display further includes an activation time display.

15. The stimulator of claim 9, further comprising a user input device for inputting timing events.

16. The stimulator of claim 15, wherein said user input device is a foot switch configured for operation by a user of said stimulator to mark transitions between phases of a seizure.

17. The stimulator of claim 9, further including an interface to a computer coupled to said digital controller for uploading timing and stimulus information for analysis.

18. A method of measuring phases of an electrically induced seizure in a test animal, comprising:

providing a stimulator capable of electrically inducing a seizure, including;

a stimulus generator for providing a stimulus;

three timers, T1, T2 and T3 coupled to said stimulus generator for measuring seizure phase duration;

a user input device coupled to said three timers for starting and stopping each of said three timers;

controls coupled to said stimulus generator for selecting current and duration of said stimulus; and

electrodes coupled to said stimulus generator configured for attachment to said test animal for delivering said stimulus;

providing a test animal;

setting a stimulus time and current using said controls;

attaching said electrodes to said test animal;

delivering said stimulus to said test animal inducing a seizure in accordance with said set stimulus time and said current

marking a transition between a first phase of said seizure and a second phase of said seizure using said user input device;

marking a transition between said second phase of said seizure and a third phase of said seizure using said user input device; and

marking the end of said third phase of said seizure.

19. The method of claim 18, wherein said test animal has been medicated with a candidate anticonvulsant drug.

20. A method of analyzing the efficacy of a candidate anticonvulsant drug by measuring phases of an electrically induced seizure in a test animal, comprising:

(a) providing a stimulator capable of electrically inducing a seizure, including;

a stimulus generator for providing a stimulus;

three timers, T1, T2 and T3 coupled to said stimulus generator for measuring duration of three seizure phases;

a user input device coupled to said three timers for starting and stopping each of said three timers;

controls coupled to said stimulus generator for selecting current and duration of said stimulus; and

electrodes coupled to said stimulus generator configured for attachment to said test animal for delivering said stimulus;

(b) providing an unmedicated test animal;

(c) setting a stimulus time and current using said controls;

(d) attaching said electrodes to said test animal;

(e) delivering said stimulus to said test animal inducing a seizure in accordance with said set stimulus time and said current

(f) marking a transition between a first phase of said seizure and a second phase of said seizure using said user input device;

(g) marking a transition between said second phase of said seizure and a third phase of said seizure using said user input device;

(h) marking the end of said third phase of said seizure;

(i) repeating steps (b) through (h) a statistically sufficient number of times to establish a baseline for each phase of a seizure;

(j) providing a test animal medicated with a candidate anticonvulsant drug and repeating steps (c) through (h) for a statistically sufficient number of times to establish a candidate drug profile; and

(k) analyzing said candidate drug profile against said baseline for reduction in seizure phase length.

21. The method of claim 20, wherein said user input device includes a foot switch.